RESUMEN
Rough implant surfaces have shown improved osseointegration rates. In a majority of dental implants, the microrough surfaces are obtained by grit blasting and/or acid-etching. The aim of this contribution was to evaluate the effects of acid-etching, after the grit-blasted treatment in titanium dental implants, on surface wettability, surface energy, osteoblast responses and its osseointegration behavior. Four surfaces were studied: as-machined, acid-etched, micro-rough by grit-blasting and the combination grit-blasted surface with acid-etched. The surfaces with increasing roughness show more osteoblastic adhered cells. This effect was most pronounced on samples blasted and blasted with acid-etching. The roughness obtained by grit-blasting is the main factor in comparison with the acid etching treatment in the biological response. These results were confirmed in vivo tests and histological analysis. The results demonstrated that the combination of the grit-blasted and acid-etched accelerated lightly bone regeneration at the different periods of implantation in comparison with the grit-blasted implants.
Asunto(s)
Grabado Ácido Dental , Implantación Dental Endoósea/instrumentación , Implantes Dentales , Oseointegración/fisiología , Titanio/química , Grabado Ácido Dental/efectos adversos , Grabado Ácido Dental/métodos , Animales , Células Cultivadas , Implantes Dentales/efectos adversos , Análisis de Falla de Equipo , Femenino , Humanos , Ensayo de Materiales , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/fisiología , Conejos , Propiedades de Superficie , Factores de Tiempo , Titanio/farmacologíaRESUMEN
The eye anatomy of six rodent species (Murinae: Apodemus sylvaticus, Mus domesticus, and Mus spretus; Arvicolinae: Clethrionomys glareolus, Arvicola terrestris and Microtus arvalis) was compared by means of light or electron microscopy to determine adaptive, and evolutive signals. Our observations revealed inter-specific morphological differences, which were moderate among representatives of the same subfamily. Specifically, traits that distinguished murines from arvicolines were the globe's relative size, the pupillary constrictor muscle, the amount of retinal epithelium melanin, and the thickness of certain ocular coats. Moreover, adaptations to new habitats and differences in temporal activity among species of the same subfamily determined discords respect to the phylogenetic patterns. This was true of the adaptations to underground conditions seen in A. terrestris, which involved the thickness of the cornea, sclera, and choroids. Likewise, A. sylvaticus had adaptations to its nocturnal lifestyle, as shown by the large overall size of the eye and lens, and by a large, thick cornea.
Asunto(s)
Arvicolinae/anatomía & histología , Ojo/anatomía & histología , Ojo/ultraestructura , Ratones/anatomía & histología , Animales , Animales Salvajes , Microscopía Electrónica/veterinariaRESUMEN
OBJECTIVE: We investigated the potentiating effect of U-46619, a synthetic analogue of thromboxane A(2) (TXA(2)), on the adrenergic responses in human saphenous vein. METHODS: Saphenous vein rings were obtained from 35 patients undergoing coronary artery bypass surgery. The rings were suspended in organ bath chambers for isometric recording of tension. RESULTS: U-46619 (10(-10)-3 x 10(-7) mol/l) produced concentration-dependent and endothelium-independent contractile responses. U-46619 (10(-10) mol/l) potentiated the contractions elicited by electrical stimulation and potassium chloride, and produced leftward shifts of the concentration-response curve for noradrenaline. The TXA(2) receptor antagonist SQ-30741 (10(-8) mol/l) prevented the potentiation evoked by U-46619. The dihydropyridine calcium antagonist nifedipine (10(-6) mol/l) did not affect the potentiation of electrical stimulation and noradrenaline induced by U-46619, but abolished the potentiation of U-46619 on KCl-induced contractions. CONCLUSIONS: U-46619 facilitates sympathetic neurotransmission and potentiates constrictor effects of noradrenaline in human saphenous veins through stimulation of TXA(2) receptors. These effects are independent of calcium entry through dihydropyridine calcium channels.
Asunto(s)
Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacología , Endotelio Vascular/efectos de los fármacos , Norepinefrina/farmacología , Receptores de Tromboxanos/antagonistas & inhibidores , Tromboxano A2/análogos & derivados , Tromboxano A2/farmacología , Vasoconstrictores/farmacología , Anciano , Bloqueadores de los Canales de Calcio/farmacología , Dihidropiridinas/metabolismo , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Estimulación Eléctrica , Endotelio Vascular/metabolismo , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Nifedipino/farmacología , Cloruro de Potasio/farmacología , Vena Safena , Estimulación QuímicaRESUMEN
To examine whether low concentrations of endothelin-1 potentiate the vasoconstrictor response to adrenergic stimulation, we recorded the isometric response of rings of rabbit pulmonary artery to electrical stimulation and noradrenaline. Endothelin-1 (10(-10) M) potentiated the contractions induced by electrical stimulation and noradrenaline. The endothelin ET(B) receptor antagonist (2,6-dimethylpiperidinecarbonyl-gamma-methyl-Leu-N(in)-[Methoxycarbonyl]-D-Trp-D-Nle) (BQ-788, 10(-6) M), but not the endothelin ET(A) receptor antagonist cyclo(D-Asp-Pro-D-Val-Leu-D-TRP) (BQ-123, 10(-6) M), inhibited the potentiating effects of endothelin-1. Pretreatment with the cyclooxygenase inhibitor indomethacin, the thromboxane synthase inhibitor furegrelate and the thromboxane receptor antagonist [1S-[1alpha,2alpha(Z),3alpha,4alpha]]-7-[3-[[[[(1-oxoheptyl)amino]acetyl]amino] methyl]-7-oxabicyclo-[2.2.1]hept-2-yl]-5-heptenoic acid (SQ-30741) (all at 10(-5) M) prevented the potentiation induced by endothelin-1 on adrenergic stimulation. The Ca(2+) channel antagonist nifedipine (10(-6) M) did not affect the potentiation induced by endothelin-1. The results indicate that endothelin-1 potentiates the responses to electrical stimulation and noradrenaline by activating endothelin ET(B) receptors. This potentiation depends on the production of cyclooxygenase-generated factors, probably thromboxane A(2).
Asunto(s)
Endotelina-1/farmacología , Norepinefrina/farmacología , Arteria Pulmonar/efectos de los fármacos , Tromboxano A2/metabolismo , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Animales , Antihipertensivos/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Masculino , Nifedipino/farmacología , Oligopéptidos/farmacología , Piperidinas/farmacología , Arteria Pulmonar/fisiología , Conejos , Receptor de Endotelina B , Receptores de Endotelina/efectos de los fármacos , Receptores de Endotelina/fisiología , Vasoconstricción/fisiologíaRESUMEN
BACKGROUND: Sildenafil is currently used in the treatment of erectile dysfunction. However, assessment of direct effects of sildenafil on coronary arteries and on arteries used as coronary grafts is unknown. This study was designed to investigate the effects of sildenafil on contracted human coronary, internal mammary, and radial arteries obtained from multiorgan donors. The observations were extended to forearm veins. Zaprinast was included in this study for comparison. METHODS: Segments of left coronary, internal mammary, and radial arteries, and forearm veins were obtained from 16 multiorgan donors. Vascular rings were suspended in organ bath chambers and isometric tension was recorded. Then the effects of sildenafil, zaprinast, and sodium nitroprusside on precontracted vessels were studied. RESULTS: Sildenafil (10(-8) - 3 x 10(-5) mol/L) caused concentration-dependent relaxation in the internal mammary arteries, radial arteries, and forearm veins. In the coronary arteries, sildenafil had a modest relaxant effect. In addition, sildenafil amplified the relaxation induced by sodium nitroprusside in all four vessels. Relaxation was unaffected by the inhibitor of nitric oxide synthase NG-monomethyl-L-arginine (10(-4) mol/L). Compared with zaprinast, sildenafil was eight to ten times more potent in terms of EC50 values. CONCLUSIONS: The direct relaxant effects of sildenafil together with its synergistic interaction with nitric oxide donors should be considered in patients undergoing coronary bypass surgery, patients with low blood pressure, and patients receiving antihypertensive regimes.
Asunto(s)
3',5'-GMP Cíclico Fosfodiesterasas/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Inhibidores de Fosfodiesterasa/farmacología , Piperazinas/farmacología , Purinonas/farmacología , Vasodilatación/efectos de los fármacos , Vasos Coronarios/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Arterias Mamarias/efectos de los fármacos , Purinas , Arteria Radial/efectos de los fármacos , Citrato de Sildenafil , Sulfonas , Venas/efectos de los fármacosRESUMEN
Sildenafil (0.1 - 30 microM), a cyclic GMP phosphodiesterase 5 (PDE 5) inhibitor, induced inhibition of electrically evoked contractions of ring segments of human vas deferens from 34 vasectomies. Zaprinast (0.1 - 100 microM), another PDE 5 inhibitor, and the nitric oxide (NO) donor sodium nitroprusside (SNP) (0.1 - 100 microM) had no effect on neurogenic contractions. The inhibition induced by sildenafil was not modified by the inhibitor of guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (1 - 30 microM) but it was abolished by the K(+) channel blockers tetraethylammonium (TEA, 1 mM), iberiotoxin (0.1 microM) and charybdotoxin (0.1 microM). Sildenafil, zaprinast and SNP did not affect the contractions induced by noradrenaline. SNP (10 microM) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10 microM) and zaprinast (100 microM). ODQ (10 microM) inhibited the increase in cyclic GMP. Sildenafil inhibits adrenergic neurotransmission in human vas deferens. The inhibition is not related to accumulation of cyclic GMP but is probably due to activation of prejunctional large-conductance Ca(2+)-activated K(+) channels.
Asunto(s)
Norepinefrina/metabolismo , Inhibidores de Fosfodiesterasa/farmacología , Piperazinas/farmacología , Transmisión Sináptica/efectos de los fármacos , Conducto Deferente/efectos de los fármacos , Adulto , GMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Contracción Muscular/efectos de los fármacos , Óxido Nítrico/fisiología , Nitroprusiato/farmacología , Norepinefrina/farmacología , Canales de Potasio/efectos de los fármacos , Canales de Potasio/fisiología , Purinas , Purinonas/farmacología , Citrato de Sildenafil , SulfonasRESUMEN
OBJECTIVES: Plasma levels of endogenous guanidino-substituted analogues of L -arginine are increased in various pathologic conditions. In the present study we determined the effects of some of these compounds on basal and stimulated release of nitric oxide in human internal thoracic and radial arteries. METHODS: Rings of human internal thoracic and radial arteries were obtained from 16 multiorgan donors. The rings were suspended in organ baths for isometric recording of tension. RESULTS: N(G)-monomethyl L -arginine (10(-6) to 10(-3) mol/L) and N(G),N(G)-dimethyl L -arginine (10(-6) to 10(-3) mol/L) caused concentration- and endothelium-dependent contractions. Maximal force of contractions for N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine in the internal thoracic artery were 18.0% +/- 4.3% and 17.8% +/- 3.8%, respectively, of the contraction to 100 mmol/L KCl, and those found in the radial artery were 9.6% +/- 2.5% and 9.1% +/- 2.4%, respectively. Aminoguanidine (10(-5) to 3 x 10(-3) mol/L) and methylguanidine (10(-5) to 3 x 10(-3) mol/L) produced endothelium-independent contractions. L -Arginine (10(-3) mol/L) prevented the contractions by N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine but did not change contractions induced by aminoguanidine and methylguanidine. N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine inhibited, in a concentration-dependent manner, the endothelium-dependent relaxation to acetylcholine in the internal thoracic artery and had little attenuating effect in the radial artery; aminoguanidine and methylguanidine were without effect. CONCLUSIONS: The results suggest that the contractions induced by N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine are due to inhibition of both basal and stimulated nitric oxide production, whereas aminoguanidine and methylguanidine do not affect the synthesis of nitric oxide. An increase in the plasma concentration of N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine is likely to represent a risk factor for abnormal vasomotor tone in conduit arteries used as coronary grafts.
Asunto(s)
Guanidinas/farmacología , Óxido Nítrico/metabolismo , Arteria Radial/efectos de los fármacos , Arterias Torácicas/efectos de los fármacos , Vasoconstrictores/farmacología , Adolescente , Adulto , Análisis de Varianza , Arginina/análogos & derivados , Arginina/farmacología , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Arteria Radial/metabolismo , Análisis de Regresión , Arterias Torácicas/metabolismoRESUMEN
OBJECTIVES: To investigate the effects of sildenafil on human penile blood vessels and evaluate the interaction of sildenafil with neurogenic-mediated responses. Sildenafil is currently used in the treatment of erectile dysfunction. METHODS: Penile dorsal arteries and deep dorsal veins were obtained from 14 multiorgan donors. Vascular rings were suspended in organ bath chambers, and the isometric tension was recorded. We then studied the effects of sildenafil on precontracted vessels and the neurogenic (noradrenergic and nitrergic) responses. RESULTS: Sildenafil (10(-9) to 3 x 10(-6) M) caused concentration-dependent relaxation and amplified the relaxation induced by sodium nitroprusside. Relaxation was unaffected by the inhibitor of nitric oxide synthase N(G)-monomethyl-L-arginine (10(-4) M). Compared with zaprinast, sildenafil was 8 to 10 times more potent in terms of the median effective concentration (EC(50)) values. Electrical field stimulation of the vessels under resting tension caused frequency-dependent contractions that were attenuated in the presence of sildenafil. When penile vessels were contracted after blockade of norepinephrine release with guanethidine (10(-6) M), electrical stimulation induced frequency-dependent, nitric oxide-dependent relaxations that were enhanced by sildenafil. CONCLUSIONS: These results indicate that the relaxation of human penile arteries and veins induced by sildenafil involves inhibition of noradrenergic contraction, enhancement of neurogenic nitric oxide-mediated relaxation, and inhibition of smooth muscle contraction.
Asunto(s)
Pene/irrigación sanguínea , Inhibidores de Fosfodiesterasa/farmacología , Piperazinas/farmacología , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Adolescente , Adulto , Arterias/efectos de los fármacos , Arterias/inervación , Humanos , Masculino , Persona de Mediana Edad , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Relajación Muscular/efectos de los fármacos , Relajación Muscular/fisiología , Purinas , Citrato de Sildenafil , Sulfonas , Vasoconstricción/fisiología , Vasodilatación/fisiología , Venas/efectos de los fármacos , Venas/inervaciónRESUMEN
OBJECTIVES: To evaluate the effects of sertraline, fluoxetine, and amitriptyline on the contractile responses of the human vas deferens muscle elicited by norepinephrine, electrical field stimulation, and KCl, because the therapeutic action of antidepressants may be accompanied by sexual dysfunction related to the contractility of the vas deferens smooth muscle. METHODS: Ring segments of the epididymal part of the vas deferens were taken from 32 elective vasectomies and mounted in organ baths for isometric recording of tension. We then studied the effects of sertraline, fluoxetine, and amitriptyline on the neurogenic and agonist-induced contractile responses. RESULTS: Amitriptyline caused concentration-dependent inhibition of neurogenic and norepinephrine-induced contractions. In contrast, only the highest concentration (10(-5) M) of sertraline and fluoxetine reduced the adrenergic contractions. The dihydropyridine calcium antagonist nifedipine (10(-6) M) completely prevented the inhibitory effect of sertraline and fluoxetine on neurogenic and norepinephrine-induced contractions but did not change the inhibition caused by amitriptyline. Sertraline, fluoxetine, and amitriptyline (all at 10(-5) M) attenuated contractions elicited by KCl and reduced contractions induced by CaCl(2) in KCl-depolarized preparations. CONCLUSIONS: The results indicate that sertraline and fluoxetine inhibit vas deferens motility through inhibition of Ca(2+) entry, with no effect on the adrenergic receptors, and amitriptyline acts as an adrenoceptor antagonist and inhibitor of the entry of calcium.
Asunto(s)
Antidepresivos/farmacología , Receptores Adrenérgicos/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Conducto Deferente/inervación , Amitriptilina/farmacología , Calcio/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Técnicas de Cultivo , Relación Dosis-Respuesta a Droga , Fluoxetina/farmacología , Humanos , Masculino , Contracción Muscular/efectos de los fármacos , Nifedipino/farmacología , Sertralina/farmacologíaRESUMEN
BACKGROUND AND PURPOSE: Accumulation of endogenous guanidino-substituted analogues of L-arginine in chronic renal failure might contribute to some of the vascular and neurological disorders of this pathology. We tested the hypothesis that in human cerebral arteries, some guanidino compounds may increase vascular tone, through nitric oxide (NO) synthase inhibition, and impair endothelium-dependent relaxation. METHODS: Rings of human middle cerebral artery were obtained during autopsy of 26 patients who had died 3 to 12 hours before. The rings were suspended in organ baths for isometric recording of tension. We then studied the responses to N(G)-monomethyl-L-arginine (L-NMMA), N(G),N(G)-dimethyl-L-arginine (asymmetrical dimethylarginine; ADMA), aminoguanidine (AG), and methylguanidine (MG). RESULTS: L-NMMA (10(-6) to 3x10(-4) mol/L) and ADMA (10(-6) to 3x10(-4) mol/L) caused concentration- and endothelium-dependent contractions (median effective concentrations [EC(50)]=1.1x10(-5) and 1.6x10(-5) mol/L, respectively; E(max)=35. 5+/-7.9% and 43.9+/-5.9% of the response to 100 mmol/L KCl). AG (10(-5) to 3x10(-3) mol/L) and MG (10(-5) to 3x10(-3) mol/L) produced endothelium-independent contractions (E(max)=44.3+/-8.8% and 45.7+/-5.8% of the response to 100 mmol/L KCl, respectively). L-Arginine (10(-3) mol/L) prevented the contractions by L-NMMA and ADMA but did not change contractions induced by AG and MG. L-NMMA and ADMA inhibited endothelium-dependent relaxation induced by acetylcholine in a concentration-dependent manner; AG and MG were without effect. CONCLUSIONS: The results suggest that the contractions induced by L-NMMA and ADMA are due to inhibition of endothelial NO synthase activity, whereas AG and MG do not affect the synthesis of NO. An increase in the plasma concentration of L-NMMA and ADMA associated with uremia is likely to represent a diminished release or effect of NO, and consequently, an increased cerebrovascular tone in uremic patients is highly conceivable.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Guanidinas/farmacología , Arteria Cerebral Media/efectos de los fármacos , Vasoconstrictores/farmacología , Vasodilatadores/farmacología , Adulto , Anciano , Arginina/análogos & derivados , Arginina/farmacología , Femenino , Humanos , Masculino , Metilguanidina/farmacología , Persona de Mediana Edad , Óxido Nítrico Sintasa/antagonistas & inhibidores , omega-N-Metilarginina/farmacologíaRESUMEN
AIMS: The therapeutic action of tricyclic agents may be accompanied by unwanted effects on the cardiovascular system. The evidence for the effects on vascular and nonvascular smooth muscle comes from animal studies. Whether these studies can be extrapolated to human vessels remains to be determined. Therefore, the present study was designed to investigate the influence of amitriptyline, nortriptyline and sertraline on the contractile responses of human isolated mesenteric arteries to electrical field stimulation, noradrenaline and potassium chloride. METHODS: Arterial segments (lumen diameter 0.8-1.2 mm) were obtained from portions of the human omentum during the course of 41 abdominal operations (22 men and 19 women), and rings 3 mm long were mounted in organ baths for isometric recording of tension. In some artery rings the endothelium was removed mechanically. RESULTS: In precontracted artery rings amitriptyline, nortriptyline and sertraline (3x10(-7)-10(-4) m ) produced concentration-dependent relaxation that was independent of the presence or absence of vascular endothelium. Incubation with indomethacin (3x10(-6) m ) reduced the pD2 values thus indicating the participation of dilating prostanoid substances in this response. Amitriptyline and nortriptyline inhibited both the neurogenic-and noradrenaline-induced contractions. In contrast, only the highest concentration of sertraline reduced the adrenergic responses. Amitriptyline, nortriptyline and sertraline inhibited contractions elicited by KCl and produced rightward shifts of the concentration-response curve to CaCl2 following incubation in calcium-free solution. CONCLUSIONS: These results indicate that amitriptyline and nortriptyline could act as adrenoceptor antagonists and direct inhibitors of smooth muscle contraction of human mesenteric arteries, whereas sertraline might principally exert its action only as direct inhibitor of smooth muscle contraction. This relaxant mechanism involves an interference with the entry of calcium.
Asunto(s)
Antidepresivos/farmacología , Arterias Mesentéricas/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Amitriptilina/farmacología , Antidepresivos de Segunda Generación/farmacología , Antidepresivos Tricíclicos/farmacología , Estimulación Eléctrica , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Contracción Muscular/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Nortriptilina/farmacología , Cloruro de Potasio/farmacología , Sertralina/farmacologíaRESUMEN
The effects of deamino-8-D-arginine vasopressin (desmopressin), a V2 receptor antidiuretic agonist, were studied in isolated rings from branches of renal arteries obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ bath chambers for isometric recording of tension. In precontracted rings with norepinephrine (10(-6) to 3 x 10(-6) mol/L), desmopressin (10(-11) to 3 x 10(-7) mol/L) caused endothelium-dependent relaxation (81%+/-4% reversal of the initial contraction in arteries with endothelium; 20%+/-4% in arteries without endothelium; P < .05). The relaxation to desmopressin in rings with endothelium was reduced significantly by indomethacin (10(-6) mol/L) and unaffected by the inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (10(-4) mol/L). Two V1 receptor antagonists (a peptidic and a nonpeptidic) had no effect on desmopressin-induced relaxation. However, V2 receptor antagonists (three peptidic and a nonpeptidic) reduced significantly (P < .05) the maximal response to desmopressin. The results of this study show that desmopressin exerts powerful endothelium-dependent relaxation of human renal arteries, probably through stimulation of V2-like receptors that may bring about the release of dilating prostaglandins.
Asunto(s)
Desamino Arginina Vasopresina/farmacología , Relajación Muscular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Receptores de Vasopresinas/fisiología , Fármacos Renales/farmacología , Arteria Renal/fisiología , Vasodilatación/efectos de los fármacos , Adulto , Anciano , Antagonistas de los Receptores de Hormonas Antidiuréticas , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Técnicas In Vitro , Indometacina/farmacología , Contracción Isométrica , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Prostaglandinas/metabolismo , Arteria Renal/citología , Arteria Renal/efectos de los fármacosRESUMEN
The present study was designed to characterize the response of human penile dorsal artery and deep dorsal vein to dilator drugs used in the diagnosis and treatment of erectile dysfunction with special emphasis on the effects on sympathetic neurotransmission. Ring segments of penile dorsal artery and deep dorsal vein were obtained from 20 multi-organ donors during procurement of organs for transplantation. The rings (3 mm long) were suspended in organ bath chambers for isometric recording of tension. We then studied the relaxant responses to prostaglandin E1 (PGE1), vasoactive intestinal peptide (VIP), papaverine (PV), sodium nitroprusside (SNP) and linsidomine chlorhydrate (SIN-1), and analysed the effects of these drugs on contractions induced by stimulation of perivascular sympathetic nerves. In artery and vein rings contracted by noradrenaline, all the drugs tested caused concentration-dependent relaxation. The order of potencies in terms of IC50 values (concentration of agonist causing 50% of the maximal relaxation) was PGE1=VIP>SNP>SIN-1=PV. Both arteries and veins contracted to electrical field stimulation (15 V, 0.5-2 Hz, 0.2 ms duration for 15 s) in a frequency-dependent manner. All relaxant drugs caused concentration-dependent inhibition of neurogenic contractions; the relative order of potencies was PGE1>VIP>SNP>SIN-1=PV. It is concluded that inhibition of sympathetic activity constitutes an effective relaxing mechanism in penile dorsal artery and vein. Modulation of sympathetic activity together with the direct effects on smooth muscle should be considered to evaluate adequately the efficacy of relaxant drugs to increase human penile blood supply.
Asunto(s)
Pene/irrigación sanguínea , Sistema Nervioso Simpático/efectos de los fármacos , Vasodilatadores/farmacología , Adolescente , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Disfunción Eréctil/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/efectos de los fármacos , Análisis de RegresiónRESUMEN
We studied the effects of vasopressin on the adrenergic responses of in vitro preparations of circular muscle from the vas deferens obtained from 28 men undergoing elective vasectomy. Vasopressin (3 x 10(-9)-3 x 10(-8) M) enhanced the phasic contractions elicited by electrical field stimulation and noradrenaline. This potentiation was blocked by the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)vasopressin (10(-6) M) but not by the vasopressin V2 receptor antagonist [d(CH2)5, D-Ile2,Ile4,Arg8]vasopressin (10(-6) M). The Ca2+ antagonist nifedipine (10(-6) M) did not affect the potentiation of electrical field stimulation induced by vasopressin and noradrenaline but reduced KCl-induced contractions and abolished the induction of phasic activity by vasopressin in the presence of KCl. The results demonstrate that vasopressin, in addition to its direct contractile effects, strongly potentiates contractions of human vas deferens elicited by adrenergic stimulation. Both the direct and indirect effects of vasopressin appear to be mediated by vasopressin V1 receptor stimulation and are independent of Ca2+ entry through dihydropyridine Ca2+ channels.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Músculo Liso/fisiología , Receptores de Vasopresinas/fisiología , Transmisión Sináptica/fisiología , Adulto , Antagonistas de los Receptores de Hormonas Antidiuréticas , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Estimulación Eléctrica , Antagonistas de Hormonas/farmacología , Humanos , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Nifedipino/farmacología , Norepinefrina , Cloruro de Potasio , Receptores de Vasopresinas/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Conducto Deferente/efectos de los fármacos , Conducto Deferente/metabolismo , Vasoconstrictores/farmacología , Vasopresinas/farmacologíaRESUMEN
We have used in vitro preparations of human penile dorsal artery and deep dorsal vein from 20 multiorgan donors to investigate whether subpressor concentrations of vasopressin facilitate noradrenergic transmission in penile blood vessels. Vasopressin constricted penile dorsal arteries (pD2, 9.38 +/- 0.18) and deep dorsal veins (pD2, 9. 40 +/- 0.14) by activating V1 receptors. Vasopressin (10(-11) and 3 x 10(-11) M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (15 V, 0.5-2 Hz, 0.2 msec duration for 15 sec) and produced leftward shifts of the concentration-response curve for norepinephrine. The V1 receptor antagonist d(CH2)5Tyr(Me)AVP (3 x 10(-9)-10(-7) M) induced concentration-dependent inhibitions of potentiation caused by vasopressin. In contrast, the V2 receptor antagonist [d(CH2)5,D-Ile2, Ile4,Arg8]-vasopressin (10(-8)-10(-7) M) did not prevent the potentiation induced by vasopressin. The results demonstrate that vasopressin exerts powerful constrictor action in human penile arteries and veins by direct stimulation of V1 receptors. In addition, vasopressin strongly potentiates the contractions to norepinephrine and stimulation of perivascular adrenergic nerves. Consequently, the direct contractile effects of vasopressin together with its amplifying effects on adrenergic-mediated constriction should be taken into consideration in the overall regulation of penile erection and in those states characterized by increased plasma vasopressin levels.
Asunto(s)
Norepinefrina/metabolismo , Pene/irrigación sanguínea , Vasoconstricción/efectos de los fármacos , Vasopresinas/farmacología , Adolescente , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Humanos , Masculino , Persona de Mediana Edad , Norepinefrina/farmacología , Receptores de Vasopresinas/fisiologíaRESUMEN
1. The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin. 2. Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant responses to electrical field stimulation and to vasoactive agents. 3. Electrical field stimulation (0.5-2 Hz) and noradrenaline (3 x 10(-10)-3 x 10(-5) M) caused frequency- and concentration-dependent contractions that were of greater magnitude in veins denuded of endothelium. The inhibitor of nitric oxide synthesis NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, l0(-4) M) increased the adrenergic responses only in rings with endothelium. 4. In preparations contracted with noradrenaline in the presence of guanethidine (10(-6) M) and atropine (10(-6) M), electrical stimulation induced frequency-dependent relaxations. This neurogenic relaxation was prevented by L-NAME, methylene blue (3 x 10(-5) M) and tetrodotoxin (10(-6) M), but was unaffected by removal of endothelium. 5. Acetylcholine (10(-8)-3 x 10(-5) M) and substance P (3 x 10(-11) -3 x 10(-7) M) induced endothelium-dependent relaxations. In contrast, sodium nitroprusside (10(-9)-3 x 10(-5) M) and papaverine (10(-8) 3 x 10(-5) M) caused endothelium-independent relaxations. 6. The results provide functional evidence that the human penile deep dorsal vein is an active component of the penile vascular resistance through the release of nitric oxide from both neural and endothelial origin. Dysfunction in any of these sources of nitric oxide should be considered in some forms of impotence.
Asunto(s)
Músculo Liso Vascular/inervación , Músculo Liso Vascular/fisiología , Pene/irrigación sanguínea , Acetilcolina/farmacología , Adolescente , Adulto , Anciano , Estimulación Eléctrica , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiología , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Contracción Muscular/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Óxido Nítrico/metabolismo , Nitroprusiato/farmacología , Norepinefrina/farmacología , Papaverina/farmacología , Sustancia P/farmacología , Vasoconstrictores/farmacología , Vasodilatadores/farmacología , Venas/efectos de los fármacos , Venas/inervación , Venas/fisiologíaRESUMEN
BACKGROUND: Arginine vasopressin (AVP) not only acts directly on blood vessels through V1 receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vivo and in vitro. The aim of the present study was to investigate whether AVP can contribute to an abnormal adrenergic constrictor response of human saphenous veins. METHODS AND RESULTS: Saphenous vein rings were obtained from 32 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. AVP (3x10[-9] mol/L) enhanced the contractions elicited by electrical field stimulation at 1, 2, and 4 Hz (by 80%, 70%, and 60%, respectively) and produced a leftward shift of the concentration-response curve to norepinephrine (half-maximal effective concentration decreased from 6.87x10[-7] to 1.04x10[-7] mol/L; P<.05). The V1 vasopressin receptor antagonist d(CH2)5Tyr(Me)AVP (10[-6] mol/L) prevented the potentiation evoked by AVP. The selective V1 receptor agonist [Phe,2 Orn8]-vasotocin (3x[-10]-9 mol/L) induced potentiation of electrical stimulation-evoked responses, which was also inhibited in the presence of the V1 receptor antagonist (10[-6] mol/L). In contrast, the V2 receptor agonist desmopressin (10[-9] to 10[-7] mol/L) did not modify neurogenic responses, and the V2 receptor antagonist [d(CH2)5, D-Ile,2 Ile,4 Arg8]-vasopressin (10[-8] to 10[-6] mol/L) did not prevent the potentiation induced by AVP. The dihydropyridine calcium antagonist nifedipine (10[-6] mol/L) did not affect the potentiating effect of AVP. CONCLUSIONS: The results suggest that low concentrations of AVP facilitate sympathetic neurotransmission and potentiate constrictor effects of norepinephrine in human saphenous veins. These effects appear to be mediated by V1 receptor stimulation and are independent of calcium entry through dihydropyridine calcium channels. Thus, AVP may contribute to vascular mechanisms involved in acute ischemic syndromes associated with venous grafts, particularly if the sympathetic nervous system is activated.
Asunto(s)
Arginina Vasopresina/fisiología , Receptores de Vasopresinas/fisiología , Vena Safena/fisiología , Anciano , Antagonistas de los Receptores de Hormonas Antidiuréticas , Bloqueadores de los Canales de Calcio/farmacología , Técnicas de Cultivo , Estimulación Eléctrica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nifedipino/farmacología , Norepinefrina/farmacología , Cloruro de Potasio/farmacología , Receptores de Vasopresinas/efectos de los fármacosRESUMEN
1. The aim of the present study was to investigate in rat mesenteric artery rings whether low concentrations of vasopressin could modify the contractile responses to noradrenaline and electrical stimulation of perivascular nerves. 2. Vasopressin (10[10]-10[-7] M) caused concentration-dependent contractions (pD2 = 8.36+/-0.09). The V1-receptor antagonist d(CH2)5Tyr(Me)AVP (10[-9]-10[-8] M) produced parallel rightward shifts of the control curve for vasopressin. Schild analysis yielded a pA2 value of 9.83 with a slope of 1.10+/-0.14. 3. Vasopressin (3 x 10[-10] and 10[-9] M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (2-8 Hz; 0.2 ms duration for 30 s) and produced leftward shifts of the concentration-response curve for noradrenaline. The V1-receptor antagonist induced concentration-dependent inhibitions of potentiation induced by vasopressin. The selective V1-receptor agonist [Phe2, Orn8]-vasotocin (3 x 10[10] and 10[-9] M) induced potentiation of electrical stimulation-evoked responses which was also inhibited in the presence of the V1 antagonist (10[-8] M). In contrast, the V2-receptor agonist deamino-8-D-arginine vasopressin (desmopressin 10[-8]-10[-7] M) did not modify the electrical stimulation-induced responses and the V2-receptor antagonist [d(CH2)5, D-Ile2, Ile4, Arg8]-vasopressin (10[-8]-10[-7] M) did not affect the potentiation evoked by vasopressin. 4. In artery rings contracted by 10(-6) M noradrenaline in the presence of 10(-6) M guanethidine and 10(-6) M atropine, electrical stimulation (2, 4 and 8 Hz) produced frequency-dependent relaxations which were unaffected by 10(-9) M vasopressin but abolished by 10(-6) M tetrodotoxin. 5. Vasopressin also potentiated contractions elicited by KCl and contractions induced by addition of CaCl2 to KCl depolarized vessels. The augmenting effects were inhibited by the V1 antagonist. 6. In the presence of the calcium antagonist nifedipine (10[-6] M), vasopressin failed to enhance the contractile responses to electrical stimulation, noradrenaline and KCl. 7. The results demonstrate that low concentrations of vasopressin strongly potentiate the contractions to adrenergic stimulation and KCl depolarization. This effect appears to be mediated by V1 receptor stimulation which brings about an increase in calcium entry through dihydropyridine-sensitive calcium channels.
Asunto(s)
Arterias Mesentéricas/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Receptores Adrenérgicos/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Vasopresinas/farmacología , Animales , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Cocaína/farmacología , Estimulación Eléctrica , Antagonistas de Hormonas/farmacología , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Nifedipino/farmacología , Norepinefrina/farmacología , Cloruro de Potasio/farmacología , Ratas , Ratas Wistar , Vasotocina/análogos & derivados , Vasotocina/farmacologíaRESUMEN
PURPOSE: The goal of this study was to determine the effects of vasopressin and the selective V2-receptor agonist desmopressin on human saphenous veins, with special emphasis on endothelium-mediated responses. METHODS: Human saphenous vein segments were obtained from 35 patients undergoing coronary bypass surgery. Paired segments, one normal and the other deendothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. Concentration-response curves to vasopressin and desmopressin were determined in the presence and in the absence of either the V1-receptor antagonist d(CH2)5Tyr (Me)AVP (10(-6) mol/L), the V1-V2-receptor antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (10(-6) mol/L), indomethacin (10(-6) mol/L), or NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10(-4) mol/L). RESULTS: In vein rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with a concentration of vasopressin producing half-maximal contractions (EC50) of 3.44 x 10(-8) mol/L. The vasopressin V1-receptor antagonist (10(-6) mol/L) displaced the control curve to vasopressin 9.86-fold to the right in a parallel manner. In precontracted vein rings previously treated with the V1-antagonist (10(-6) mol/L) vasopressin caused endothelium-dependent relaxations. This relaxation was reduced significantly by indomethacin (10(-6) mol/L) and unaffected by the V1-V2-receptor antagonist (10(-6) mol/L) or by L-NAME (10(-4) mol/L). Desmopressin caused endothelium-dependent relaxations in precontracted vein rings that were inhibited by the mixed V1-V2-receptor antagonist and by indomethacin, but not by the V1-antagonist or by pretreatment with L-NAME. CONCLUSIONS: These observations indicate that vasopressin exerts contractile effects on human saphenous vein by V1-receptor stimulation. Vasopressin causes dilatation of human saphenous vein only if V1-receptor blockade is present. This relaxation appears to be mediated by the release of relaxant prostaglandins, probably derived from endothelial cells, and is independent of V2-receptor stimulation or release of nitric oxide. Desmopressin elicits relaxation that is largely dependent on V2-receptor stimulation, which may bring about the release of dilating prostaglandins from the endothelial cells.
Asunto(s)
Desamino Arginina Vasopresina/farmacología , Endotelio Vascular/efectos de los fármacos , Vena Safena/efectos de los fármacos , Vasoconstrictores/farmacología , Vasopresinas/farmacología , Adulto , Anciano , Antagonistas de los Receptores de Hormonas Antidiuréticas , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Desamino Arginina Vasopresina/administración & dosificación , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Femenino , Antagonistas de Hormonas/farmacología , Humanos , Indometacina/farmacología , Contracción Isométrica , Masculino , Persona de Mediana Edad , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Prostaglandinas/farmacología , Receptores de Vasopresinas/agonistas , Vasoconstrictores/administración & dosificación , Vasodilatadores/farmacología , Vasopresinas/administración & dosificación , Vasotocina/análogos & derivados , Vasotocina/farmacologíaRESUMEN
Vasopressin not only acts directly on blood vessels through V1-receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vitro and in vivo. The aim of the present study was to investigate whether subpressor concentrations of vasopressin could modify the constrictor responses to norepinephrine and electrical stimulation of the perivascular nerves in human mesenteric arteries. Human mesenteric artery rings (3-3.5 mm long, 0.8-1.2 mm OD) were obtained from 38 patients undergoing abdominal operations. The arterial rings were suspended in organ bath chambers for isometric recording of tension. Vasopressin (3 x 10(-11) M) enhanced the contractions elicited by electrical stimulation at 2, 4, and 8 Hz (by 100, 100, and 72%, respectively) and produced a leftward shift of the concentration-response curves to norepinephrine (half-maximal effective concentration decreased from 2.2 x 10(-6) to 5.0 x 10(-7) M; P < 0.05) without any alteration in maximal contractions. Vasopressin also potentiated KCl- and calcium-induced contractions. The V1-receptor antagonist 1-[beta-mercapto-beta,beta-cyclopentamethylenepropionic acid-2-O-methyl-tyrosine, 8-arginine]vasopressin (10(-6) M) prevented the potentiation evoked by vasopressin in all cases. The calcium antagonist nifedipine (10(-6) M) did not affect the potentiation of electrical stimulation and norepinephrine induced by vasopressin but abolished KCl-induced contractions. The results suggest that vasopressin, in addition to its direct vasoconstrictor effect, strongly potentiates the responses to adrenergic stimulation and KCl depolarization. Both the direct and indirect effects of vasopressin appear to be mediated by V1-receptor stimulation. The amplifying effect of vasopressin on constrictor responses may be relevant in those clinical situations characterized by increased plasma vasopressin levels.