RESUMEN
La oxitocina (OXT) como la arginina-vasopresina (AVP) son dos hormonas primitivas secretadas por la hipófisis posterior. Sus receptores están mucho más ampliamente distribuidos en el organismo de lo que se pensaba originalmente, incluido el hueso. En los estudios preclínicos, la OXT ha mostrado ser anabólica para el hueso, promoviendo la osteogénesis sobre la adipogénesis y favoreciendo la actividad osteoblástica sobre la osteoclástica. Tanto los osteoblastos como los osteoclastos tienen receptores para la OXT, y los efectos de los estrógenos sobre la masa ósea en ratones está mediada por lo menos en parte por la OXT. El mecanismo preciso por el cual la activación de los receptores de oxitocina (OXTR) se traduce en un incremento de la formación ósea permanece poco claro. La AVP también podría afectar el esqueleto en forma directa. Dos de los receptores de la AVP, V1a y V2 están expresados en osteoblastos y osteoclastos. La inyección de AVP en ratones de tipo salvaje aumenta la formación osteoclastos que producen resorción y reduce los osteoblastos formadores de hueso. En forma opuesta, la exposición de precursores osteoblásticos a antagonistas de los receptores V1a o V2, incrementan la osteoblastogénesis, como también lo hace la deleción genética del receptor V1a. (AU)
Both oxytocin (OXT) and argininevasopressin (AVP) are primitive hormones secreted by the posterior pituitary gland. OXT receptors are much more widely distributed in the body than originally thought, including in bone. In preclinical studies, OXT has been shown to be anabolic for bone, promoting osteogenesis over adipogenesis and favoring osteoblastic over osteoclastic activity. Both osteoblasts and osteoclasts have receptors for OXT, and the effects of estrogen on bone mass in mice is mediated at least in part by OXT. The precise mechanism by which the activation of oxytocin receptors (OXTRs) results in an increase in bone formation remains unclear. AVP could also have direct actions on the skeleton. The two AVP receptors, V1a and V2, are expressed in osteoblasts and osteoclasts. Injection of AVP in wild-type mice increases the formation of osteoclasts increasing bone resorption, and reduces bone-forming osteoblasts. On the contrary, the exposure of osteoblastic precursors to V1a and V2 antagonists increase osteoblastogenesis, the same as the genetic deletion of the V1a receptor. (AU)
Asunto(s)
Humanos , Animales , Ratones , Hormonas Neurohipofisarias/biosíntesis , Arginina Vasopresina/efectos adversos , Oxitocina/uso terapéutico , Osteoblastos/fisiología , Osteoclastos/fisiología , Osteogénesis , Osteoporosis/terapia , Hormonas Neurohipofisarias/fisiología , Arginina Vasopresina/antagonistas & inhibidores , Arginina Vasopresina/biosíntesis , Arginina Vasopresina/fisiología , Arginina Vasopresina/uso terapéutico , Oxitocina/biosíntesis , Oxitocina/efectos adversos , Oxitocina/fisiología , Transducción de Señal , Densidad Ósea , Densidad Ósea/efectos de los fármacos , Receptores de Oxitocina/biosíntesis , Receptores de Oxitocina/fisiología , Estradiol/uso terapéutico , Estrógenos/fisiologíaRESUMEN
The neuropeptide arginine vasopressin (AVP) exerts a modulatory role on hippocampal excitability through vasopressin V(1A) and V(1B) receptors. However, the origin and mode of termination of the AVP innervation of the hippocampus remain unknown. We have used light and electron microscopy to trace the origin, distribution and synaptic relationships of AVP-immuno-positive fibres and nerve terminals in the rat hippocampus. Immuno-positive fibres were present in all areas (CA1-3, dentate gyrus) of the whole septo-temporal extent of the hippocampus; they had the highest density in the CA2 region, strongly increasing in density towards the ventral hippocampus. Two types of fibres were identified, both establishing synaptic junctions. Type A had large varicosities packed with immuno-positive large-granulated peptidergic vesicles and few small clear vesicles forming type I synaptic junctions with pyramidal neuron dendrites, dendritic spines and with axonal spines. Type B had smaller varicosities containing mostly small clear vesicles and only a few large-granulated vesicles and established type II synaptic junctions mainly with interneuron dendrites. The AVP-positive axons in stratum oriens appeared to follow and contact metabotropic glutamate receptor 1α (mGluR1α)-immuno-positive interneuron dendrites. Fluoro-Gold injection into the hippocampus revealed retrogradely labelled AVP-positive somata in hypothalamic supraoptic and paraventricular nuclei. Hypothalamo-hippocampal AVP-positive axons entered the hippocampus mostly through a ventral route, also innervating the amygdala and to a lesser extent through the dorsal fimbria fornix, in continuation of the septal AVP innervation. Thus, it appears the AVP-containing neurons of the magnocellular hypothalamic nuclei serve as important sources for hippocampal AVP innervation, although the AVP-expressing neurons located in amygdala and bed nucleus of the stria terminalis reported previously may also contribute.
Asunto(s)
Arginina Vasopresina/análisis , Hipocampo/química , Hipotálamo Anterior/química , Fibras Nerviosas Mielínicas/química , Núcleo Hipotalámico Paraventricular/química , Sinapsis/química , Animales , Arginina Vasopresina/fisiología , Hipocampo/fisiología , Hipotálamo Anterior/fisiología , Masculino , Fibras Nerviosas Mielínicas/fisiología , Vías Nerviosas/química , Vías Nerviosas/fisiología , Núcleo Hipotalámico Paraventricular/fisiología , Ratas , Ratas Wistar , Sinapsis/fisiologíaRESUMEN
We speculated that the influence of lateral preoptic area (LPO) in sodium balance, involves arginine8-vasopressin (AVP) and angiotensin (ANG II) on Na+ uptake in LPO. Therefore, the present study investigated the effects of central administration of specific AVP and ANG II antagonists (d(CH2)5-Tyr (Me)-AVP (AAVP) and [Adamanteanacetyl1, 0-ET-d-Tyr2, Val4, Aminobutyryl6, Arg(8,9)]-AVP (ATAVP) antagonists of V1 and V2 receptors of AVP. Also the effects of losartan and CGP42112A (selective ligands of the AT1 and AT2 angiotensin receptors, respectively), was investigated on Na+ uptake and renal fluid and electrolyte excretion. After an acclimatization period of 7 days, the animals were maintained under tribromoethanol (200 mg/kg body weight, intraperitonial) anesthesia and placed in a Kopf stereotaxic instrument. Stainless guide cannula was implanted into the LPO. AAVP and ATAVP injected into the LPO prior to AVP produced a reduction in the NaCl intake. Both the AT1 and AT2 ligands administered into the LPO elicited a decrease in the NaCl intake induced by AVP injected into the LPO. AVP injection into the LPO increased sodium renal excretion, but this was reduced by prior AAVP administration. The ATAVP produced a decreased in the natriuretic effect of AVP. The losartan injected into LPO previous to AVP decreased the sodium excretion and the CGP 421122A also decreased the natriuretic effect of AVP. The AVP produced an antidiuresis effect that was inhibited by prior administration into LPO of the ATAVP. The AAVP produced no change in the antidiuretic effect of AVP. These results suggest that LPO are implicated in sodium balance that is mediated by V1, V2, AT1 and AT2 receptors.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Antagonistas de Receptores de Angiotensina , Arginina Vasopresina/antagonistas & inhibidores , Receptores de Vasopresinas/administración & dosificación , Sodio/metabolismo , Angiotensina II/antagonistas & inhibidores , Animales , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/farmacología , Arginina Vasopresina/fisiología , Presión Sanguínea , Relación Dosis-Respuesta a Droga , Hipotálamo/metabolismo , Inyecciones Intraventriculares , Losartán/farmacología , Masculino , Oligopéptidos/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Angiotensina/fisiologíaRESUMEN
BACKGROUND AND OBJECTIVES: The aim of this work was to study the effects of low intensity laser radiation on water transport in the toad bladder in vitro. STUDY DESIGN/MATERIALS AND METHODS: The water flow through the membrane was measured gravimetrically in bag preparations of the membrane. RESULTS: Laser radiation did not alter the water transport in the presence nor in the absence of vasopressin. In contrast, when the hemibladders were previously treated with vasopressin, the laser decreased by approximately 33.70% arginine-vasopressin (AVP)-mediated water transport. Laser radiation increased 3'5'-cyclic adenosine monophosphate (3'5'-cAMP) mediated water transport by approximately 23%. The association of laser radiation with indomethacin (IND) did not affect AVP-mediated water transport. CONCLUSIONS: This data suggests that the laser may have two effects on AVP-mediated water transport: one inhibitory effect on 3'5'-cAMP synthesis by inhibiting the adenylate cyclase complex and another stimulatory effect by inhibiting nucleotide-phosphodiesterase activity. Our results also indicate that the laser does not interfere in the prostaglandins biosynthesis induced by AVP.
Asunto(s)
Terapia por Luz de Baja Intensidad , Vejiga Urinaria/efectos de la radiación , Animales , Arginina Vasopresina/fisiología , Transporte Biológico/efectos de la radiación , Bufo marinus , Indometacina/farmacología , Masculino , Equilibrio Hidroelectrolítico/efectos de la radiaciónRESUMEN
Arginine vasopressin (AVP) is a nonapeptide long known as an endocrine and paracrine regulator of important systemic functions, namely, vasoconstriction, gluconeogenesis, corticosteroidogenesis, and excretion of water and urea. Here we report, for the first time, that AVP specifically inhibits expression of the cyclin D1 gene, leading to cell cycle blockage and halting cell proliferation. In G0/G1-arrested mouse Y1 adrenocortical tumor cells, maintained in serum-free medium (SFM), AVP mimics FGF2, promoting rapid ERK1/2 activation (5 min) followed by c-Fos protein induction (2 h). PKC inhibitor Go6983 and PI3K inhibitors wortmannin and LY294002 all inhibit ERK1/2 activation by AVP, but not by FGF2. Thus, AVP and FGF2 concur to activate ERK1/2 by different regulatory pathways. However, AVP is not a mitogenic factor for Y1 cells. On the contrary, AVP strongly antagonizes FGF2 late induction (2-5 h) of the cyclin D1 gene, down-regulating both cyclin D1 mRNA and protein. AVP inhibition of cyclin D1 expression is sufficient to block G1 phase progression and cell entry into the S phase, monitored by BrdU nuclear labeling. In addition, AVP completely inhibits proliferation of Y1 cells in 10% fetal calf serum (10% FCS) medium. On the other hand, ectopic expression of the cyclin D1 protein renders Y1 cells resistant to AVP for both entry into the S phase in SFM and continuous proliferation in 10% FCS medium. In conclusion, inhibition of cyclin D1 expression by AVP is an efficient mechanism of cell cycle blockage and consequent proliferation inhibition in Y1 adrenocortical cells.
Asunto(s)
Arginina Vasopresina/fisiología , Ciclo Celular/fisiología , Ciclina D1/antagonistas & inhibidores , Ciclina D1/biosíntesis , Regulación de la Expresión Génica/fisiología , Inhibidores de Crecimiento/fisiología , Células Tumorales Cultivadas/metabolismo , Células Tumorales Cultivadas/patología , Neoplasias de la Corteza Suprarrenal/enzimología , Neoplasias de la Corteza Suprarrenal/metabolismo , Neoplasias de la Corteza Suprarrenal/patología , Animales , Arginina Vasopresina/farmacología , Ciclo Celular/efectos de los fármacos , Células Clonales , Medios de Cultivo Condicionados , Ciclina D1/genética , Resistencia a Antineoplásicos , Activadores de Enzimas/farmacología , Factor 2 de Crecimiento de Fibroblastos/farmacología , Fase G1/efectos de los fármacos , Fase G1/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Inhibidores de Crecimiento/farmacología , Ratones , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Imitación Molecular , Fosfatidilinositol 3-Quinasas/fisiología , Proteína Quinasa C/fisiología , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Fase de Descanso del Ciclo Celular/fisiología , Transfección , Células Tumorales Cultivadas/enzimologíaRESUMEN
The presence of both CFTR and ClC-2 proteins in the kidney suggest that they are involved in chloride transport along the nephron but their physiological roles in this organ are not known. To further understand the role of these chloride channels we studied Wistar rats subjected to dehydration for 2 days and also the homozygous Brattleboro rats, a strain of Long-Evans rats carrying an autosomal recessive mutation that leads to a deficiency of arginine-vasopressin (AVP) secretion in the plasma. The expression of CFTR was increased in the medulla of dehydrated Wistar rats and no variation was observed in the cortex. The expression of both ClC-2 and CFTR mRNAs was low in the renal cortex and medulla of the homozygous Brattleboro rats but returned to normal levels after AVP reposition. By the use of Madine-Darby canine kidney (MDCK) type I epithelial cells, it was observed that AVP (10(-8), 10(-7) and 10(-6) M) increased CFTR mRNA expression "in vitro" but no effect was observed when changes in the medium tonicity were caused by the addition of sucrose, NaCl, manitol or urea. The modulation of both CFTR and ClC-2 mRNA by AVP, the main hormone involved in the regulation of body fluid osmolality, suggests the participation of these two chloride channels in the renal tubule transcellular chloride transport modulated by AVP.
Asunto(s)
Arginina Vasopresina/fisiología , Canales de Cloruro/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Médula Renal/metabolismo , Animales , Sangre/metabolismo , Western Blotting , Canales de Cloruro CLC-2 , Línea Celular , Deshidratación/metabolismo , Perros , Homocigoto , Riñón/metabolismo , Corteza Renal/metabolismo , Concentración Osmolar , ARN Mensajero/metabolismo , Ratas , Ratas Brattleboro/genética , Ratas Long-Evans , Ratas Wistar , Receptores de Vasopresinas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Orina/químicaRESUMEN
O diabetes insipidus nefrogênico (DIN) é uma doença rara caracterizada pela incapacidade do rim de concentrar a urina, a despeito de concentrações normais ou aumentadas do hormônio antidiurético arginina-vasopressina (AVP). Recentes avanços da fisiopatologia renal mostraram que, após a ligação do AVP ao seu receptor AVPR2 (receptor de vasopressina tipo 2), uma cascata de eventos culmina com a reabsorção de água no túbulo coletor, por meio de canais permeáveis exclusivamente à água e localizados nas membranas apicais do túbulo coletor, sendo o mais importante deles a aquaporina-2 (AQP2). A identificação, caracterização e análise mutacional dos genes AVPR2 e AQP2 permitiram estabelecer as bases moleculares de vários tipos hereditários de diabetes insipidus nefrogênico. Aproximadamente 90 por cento desses pacientes apresentam mutações do AVPR2, 8 por cento apresentam mutações no AQP2 e o restante não tem causas identificadas. Nessa revisão apresentamos exemplos de alterações genéticas e sugerimos que o uso de técnicas de biologia molecular pode minimizar as complicações dessa doença heterogênea mas com fenótipo bastante semelhante.
Asunto(s)
Humanos , Masculino , Femenino , Diabetes Insípida Nefrogénica/diagnóstico , Diabetes Insípida Nefrogénica/fisiopatología , Acuaporinas/genética , Arginina Vasopresina/fisiología , Diabetes Insípida Nefrogénica/genética , Mutación , Linaje , Receptores de Vasopresinas/genéticaRESUMEN
Vasopressin and bradykinin are two of the most important peptides in regulating vascular tone, water, and ionic balance in the body, and thus they play a key role in controlling blood pressure. In addition to being a potent vasoconstrictor, Vasopressin also has an antidiuretic activity in the kidney, whereas kinins regulate renal blood flow in addition to their vasodilatory and natriuretic activity. We review here the primary evidence for the localization of the vasopressin and kinin receptors and their role in ionic and water regulation in the kidney.
Asunto(s)
Arginina Vasopresina/fisiología , Túbulos Renales/metabolismo , Receptores de Bradiquinina/fisiología , Receptores de Vasopresinas/fisiología , Animales , Humanos , Sistema Calicreína-Quinina/fisiología , Cininas/metabolismo , Potasio/metabolismo , Sodio/metabolismoRESUMEN
Vasopressin and bradykinin are two of the most important peptides in regulating vascular tone, water, and ionic balance in the body, adn thus they play a key role in controlling blood pressure. In addition to being a potent vasoconstrictor, Vasopressin also has an antidiuretic activity in the kidney, whereas kinins regulate renal blood flow in addition to their vasodilatory and natriuretic activity. We review here the primary evidence for the localization of the vasopressin and kinin receptors and their role in ionic and water regulation in the kidney.
Asunto(s)
Humanos , Animales , Arginina Vasopresina/fisiología , Túbulos Renales/metabolismo , Receptores de Bradiquinina/fisiología , Receptores de Vasopresinas/fisiología , Sistema Calicreína-Quinina/fisiología , Cininas/metabolismo , Potasio/metabolismo , Sodio/metabolismoRESUMEN
It has been reported that arginine vasopressin (AVP) plays a thermoregulatory action, but very little is known about the mechanisms involved. In the present study, we tested the hypothesis that nitric oxide (NO) plays a role in systemic AVP-induced hypothermia. Rectal temperature was measured before and after AVP, AVP blocker, or NG-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor) injection. Control animals received saline injections of the same volume. The basal body temperature (Tb) measured in control animals was 36.53 +/- 0.08 degreesC. We observed a significant (P < 0.05) reduction in Tb to 35.44 +/- 0.19 degreesC after intravenous injection of AVP (2 micrograms/kg) and to 35.74 +/- 0. 10 degreesC after intravenous injection of L-NAME (30 mg/kg). The systemic injection of the AVP blocker [beta-mercapto-beta, beta-cyclopentamethylenepropionyl1,O-Et-Tyr2,Val4,Arg8]vasopressin (10 micrograms/kg) caused a significant increase in Tb to 37.33 +/- 0.23 degreesC, indicating that AVP plays a tonic role by reducing Tb. When the treatments with AVP and L-NAME were combined, systemically injected L-NAME blunted AVP-induced hypothermia. To assess the role of central thermoregulatory mechanisms, a smaller dose of L-NAME (1 mg/kg) was injected into the third cerebral ventricle. Intracerebroventricular injection of L-NAME caused an increase in Tb, but when intracerebroventricular L-NAME was combined with systemic AVP injection (2 micrograms/kg), no change in Tb was observed. The data indicate that central NO plays a major role mediating systemic AVP-induced hypothermia.
Asunto(s)
Arginina Vasopresina/fisiología , Regulación de la Temperatura Corporal/fisiología , Temperatura Corporal/fisiología , Ventrículos Cerebrales/fisiología , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/fisiología , Animales , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/farmacología , Temperatura Corporal/efectos de los fármacos , Regulación de la Temperatura Corporal/efectos de los fármacos , Ventrículos Cerebrales/efectos de los fármacos , Antagonistas de Hormonas/farmacología , Hipotermia Inducida , Inyecciones Intraventriculares , Masculino , NG-Nitroarginina Metil Éster/administración & dosificación , Ratas , Ratas WistarRESUMEN
Our objective was to study the role of vasopressinergic synapses at the nucleus tractus solitarii (NTS) in the modulation of exercise-induced tachycardia. We evaluated the effect of NTS administration of vasopressin (AVP) or vasopressin antagonist (AVP(ant)) on heart rate (HR) and mean arterial pressure (MAP) responses during dynamic exercise in male rats with chronic arterial and NTS cannulas. Sedentary (S) and trained (T) animals were tested at three or four exercise levels (from 0.4 up to 1.4 km/h) after NTS injection of AVP or AVP(ant) 20-30 min before treadmill exercise. Plasma and regional brain levels of AVP were measured in separate groups of S and T rats at rest and immediately after acute exercise. When administered into the NTS, exogenous AVP (20 pmol) caused a small but significant decrease in baseline HR and potentiated the tachycardiac response to mild to moderate exercise intensities (on average, increases of 35-46 beats/min over control tachycardic response). The potentiation of exercise tachycardia by AVP was long lasting and more pronounced in T than in S rats. Even 2 days after NTS AVP injection, there was evidence for an alteration in the HR response to exercise. Mediation by V1 receptors was supported by the blunted tachycardiac response to exercise after administration of a V1 antagonist d(CH2)5Tyr MeAVP into the NTS in both T and S rats (average reductions of 23-34 and 13-19 beats/min below control tachycardia, respectively). No changes were observed in baseline MAP or the exercise-induced pressor responses. There were specific changes in brain stem AVP levels that were related to the exercise treatment. T rats showed a marked increase in dorsal and ventral brain stem AVP content after acute exercise. There were no changes in hypothalamus, median eminence, posterior pituitary, or plasma AVP. These data indicate that vasopressinergic synapses and V1 receptors in the NTS are involved in the potentiation of tachycardic response to exercise. The vasopressinergic mechanism operates in both S and T rats, but training alters the sensitization of V1 receptors by AVP.
Asunto(s)
Arginina Vasopresina/fisiología , Frecuencia Cardíaca/fisiología , Actividad Motora/fisiología , Núcleo Solitario/metabolismo , Animales , Arginina Vasopresina/antagonistas & inhibidores , Arginina Vasopresina/farmacología , Presión Sanguínea/fisiología , Encéfalo/metabolismo , Masculino , Microinyecciones , Ratas , Ratas Endogámicas WKYRESUMEN
OBJECTIVE: To assess the plasma levels and action of arginine vasopressin (AVP) in patients with Cushing's disease. There are many reports that patients with Addison's disease have increased AVP levels associated with hyponatraemia and hypoosmolality, but none on the dynamics of secretion of this neurohormone during osmolality-based stimulation in patients with chronic hypercortisolism. DESIGN AND SUBJECTS: The plasma AVP concentration and the urinary and plasma osmolality after a 7.5-h water deprivation test (WDT) were evaluated in 13 patients with Cushing's disease and 15 normal (control) individuals. In patients with Cushing's disease we also assessed the urinary osmolality in response to 10 micrograms i.v. desmopressin (DDAVP) administered at the end of the WDT. RESULTS: At the end of the WDT, urinary osmolality was significantly lower in patients with Cushing's disease (511.5 +/- 148.5 mOsm/l) than in the normal subjects (981.1 +/- 107.1 mOsm/l, P < 0.001), whereas plasma osmolality did not differ between the two groups. Consequently, the urine/plasma osmolality ratio (Uosm/Posm) was lower in patients with Cushing's disease than in normal individuals (1.8 +/- 0.5 compared with 3.4 +/- 0.4, P < 0.001). The AVP concentration also was greater (7.3 +/- 3.1 pmol/l) in those with Cushing's disease than in the controls (3.9 +/- 2.3 pmol/l, P < 0.005). After administration of DDAVP to the hypercortisolaemic patients, the urinary osmolality attained (718.0 +/- 200.0 mOsm/l) was still lower than that in the normal group at the end of WDT (P < 0.005). CONCLUSIONS: Patients with Cushing's disease presented higher AVP levels and smaller Uosm/Posm ratios than normal subjects. After DDAVP, the patients with Cushing's disease were unable to concentrate the urine adequately. These data suggest that the kidney shows resistance to the action of both endogenous and exogenous AVP in patients with Cushing's disease.
Asunto(s)
Arginina Vasopresina/fisiología , Síndrome de Cushing/tratamiento farmacológico , Desamino Arginina Vasopresina/uso terapéutico , Riñón/efectos de los fármacos , Adulto , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/sangre , Sangre/metabolismo , Síndrome de Cushing/sangre , Síndrome de Cushing/orina , Resistencia a Medicamentos , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Concentración Osmolar , Valores de Referencia , Orina/química , Privación de AguaRESUMEN
Studies in our laboratory and others have demonstrated that arginine vasopressin (AVP) exerts potent vasoconstrictor actions on the vessels supplying the renal medulla. The physiological importance of these vascular effects of AVP has been difficult to assess because of high endogenous levels of AVP in anesthetized, surgically prepared animals. We have developed a decerebrated, hypophysectomized, renal-denervated rat model that enables us to study the effects of low levels of AVP on the pressure-diuresis, relationship under acute conditions. These rats maintain normal mean arterial pressure (MAP) and plasma AVP (2.5 pg/ml). Cortical and medullary blood flow (CBF and MBF, respectively) were measured by laser-Doppler flowmetry and total renal blood flow (RBF) by transit time flowmetry. Renal interstitial fluid pressure (RIFP) and urinary sodium excretion (UNaV) responses were determined during controlled increases of MAP produced by aortic occlusion below the renal arteries. From a baseline of 97 +/- 2 mmHg, 30% increases in MAP resulted in a 63% increase in MBF, 35% increase in RIFP, and sixfold increase in UNaV, whereas CBF and RBF remained unchanged. Infusion of AVP (0.50 ng.kg-1.min-1, which increased plasma AVP from normal control levels of 3 pg/ml to 11 pg/ml) produced no change in baseline MAP, RBF, or CBF but lowered MBF by 24%, RIFP by 26%, and UNaV by 71%. The slope of the relationship of AP and UNaV, MBF, and RIP was reduced to nearly zero by these small increases of plasma AVP. We conclude that an increase of plasma AVP in the range that occurs with water restriction decreases MBF selectively and greatly attenuates the arterial pressure-MBF and pressure-natriuretic relationship.
Asunto(s)
Arginina Vasopresina/fisiología , Presión Sanguínea , Diuresis , Médula Renal/fisiología , Natriuresis , Animales , Proteínas Sanguíneas/metabolismo , Estado de Descerebración , Gases/sangre , Hematócrito , Concentración de Iones de Hidrógeno , Presión Hidrostática , Corteza Renal/irrigación sanguínea , Corteza Renal/fisiología , Médula Renal/irrigación sanguínea , Masculino , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional , Equilibrio HidroelectrolíticoRESUMEN
Experiments were performed in unanesthetized rats to determine responses to 48 h water restriction of the renal regional microcirculation (cortex, outer medulla, and inner medulla) using implanted optical fibers and laser-Doppler flowmetry. The role of vasopressin (AVP) as a mediator of renal regional blood low changes and its contribution to urinary concentrating ability were assessed by continuous intramedullary interstitial infusion of specific V1 receptor antagonist d(CH2)5 [Tyr-(Me)2, Ala-NH2]AVP (2ng . kg-1 . min-1). Inner medullary blood flow decreased 34% at the end of 48 h of water restriction, whereas cortical and outer medullary flow did not change. This fall in inner medullary blood flow was substantially attenuated (18%) by the continuous interstitial infusion of the antagonist. Plasma AVP levels increased from control levels of 3.4 +/- 1.1 to 20.5 +/- 5.4 pg/ml (P < 0.05) by the end of the 48-h period of water restriction. Arterial pressure increased slightly but significantly during water restriction in the control rats. Infusion of antagonist impaired the maximal urinary concentrating ability, as demonstrated by the lower urine osmolality in this group than in the control group (1,893 +/- 49 vs. 2,419 +/- 225 mosmol/kg H2O; P < 0.05) measured during the second day of water restriction. Sodium and urea concentration decreased 20 and 22%, respectively, indicating that both contributed to the lower urine osmolality observed in the group of rats receiving the antagonist. We conclude that water restriction induces a selective decrease in inner medullary blood flow, which is mediated almost completely by endogenously released AVP. This vascular effect of AVP contributes to the maximum concentrating ability of the kidney.
Asunto(s)
Arginina Vasopresina/fisiología , Circulación Renal , Privación de Agua/fisiología , Animales , Arginina Vasopresina/sangre , Hemodinámica , Capacidad de Concentración Renal , Corteza Renal/irrigación sanguínea , Médula Renal/irrigación sanguínea , Flujometría por Láser-Doppler , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
We investigated the genesis of the hypertensive response to acute (45 min) aortic constriction in two models of chronic vasopressin (AVP) deficiency, i.e., Brattleboro strain and median eminence lesioned (MEL) Wistar rats. The same degree of partial aortic constriction, with a pneumatic cuff placed around the abdominal aorta, yielded a sudden and maintained increase in carotid pressure to the same extent in Brattleboro, MEL and sham-MEL rats. Blockage of AVP V1 receptors with d(CH2)5Tyr[Me]AVP did not affect the hypertensive response of Brattleboro or MEL rats, but gradually blunted the response of sham-MEL rats. Blockage of angiotensin II receptors with saralasin blunted the hypertensive response of the AVP-deficient subjects throughout the experiment, but only delayed (5-15 min) the onset of hypertension in sham-MEL rats. Simultaneous blockage of AVP and angiotensin II blunted the hypertensive response of sham-MEL and AVP-deficient rats throughout the experiment. These data demonstrate that when one vasoactive system is chronically absent, as is the case for AVP in Brattleboro and MEL rats, the renin-angiotensin system plays the major role in the pathophysiology of acute aortic coarctation hypertension.
Asunto(s)
Coartación Aórtica/complicaciones , Arginina Vasopresina/deficiencia , Hipertensión/etiología , Antagonistas de Receptores de Angiotensina , Animales , Antagonistas de los Receptores de Hormonas Antidiuréticas , Coartación Aórtica/fisiopatología , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/farmacología , Arginina Vasopresina/fisiología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Enfermedad Crónica , Femenino , Antagonistas de Hormonas/farmacología , Hipertensión/fisiopatología , Masculino , Eminencia Media/lesiones , Ratas , Ratas Brattleboro , Ratas Wistar , Sistema Renina-Angiotensina/fisiología , Saralasina/farmacologíaRESUMEN
Arginine vasopressin (AVP) has been found to participate in blood pressure maintenance especially when other pressor systems are endogenously or pharmacologically impaired. The purpose of this study was to assess the pressor contribution of AVP to orthostatic blood pressure maintenance in otherwise healthy patients with essential hypertension. Twenty-seven patients were grouped according to age (young n = 13, elderly n = 14) and race (white n = 13, black n = 14). Integrity of autonomic nervous system (ANS) was assessed by Valsalva's maneuver, cold pressor test and head-up tilt. AVP contribution to blood pressure was estimated by the fall in mean arterial pressure in response to IV injection of 0.5 mg of a V1 AVP inhibitor (AVPi). Elderly subjects were found to have a mild (subclinical) ANS impairment as indicated by absence of bradycardia in phase 4 of Valsalva's maneuver and hypotension without concurrent tachycardia during head up tilt. Depressor responses to AVPi while subjects were in the upright position, were greater in elderly and blacks (-15 +/- 11 mm Hg and -15 +/- 12 mm Hg, respectively, P < .05) than young and whites (-8 +/- 6 and -7 +/- 6 mm Hg, respectively, ns). The greater importance of the AVP component in the elderly may be at least partially explained by a mild ANS impairement, whereas hormonal characteristics of hypertension in blacks may explain greater AVPi induced fall in mean arterial pressure. Our data show that both age and race influence the response to AVPi.
Asunto(s)
Arginina Vasopresina/fisiología , Presión Sanguínea/fisiología , Hipertensión/fisiopatología , Postura/fisiología , Adulto , Anciano , Envejecimiento/fisiología , Arginina Vasopresina/sangre , Sistema Nervioso Autónomo/fisiopatología , Población Negra , Frío , Frecuencia Cardíaca/fisiología , Humanos , Persona de Mediana Edad , Radioinmunoensayo , Maniobra de Valsalva , Población BlancaRESUMEN
We sought to determine whether arginine vasopressin (AVP) modulates arterial pressure (AP) by a receptor-mediated action in the nucleus reticularis rostroventrolateralis (nRVL). Immunocytochemical labeling with an antiserum against a synthetic AVP conjugate revealed a discrete although modest presumptive neuropeptidergic innervation of the nRVL. Electron microscopic analysis of vasopressinergic processes in the nRVL revealed that AVP-like immunoreactivity (AVP-LI) was primarily in axons and axon terminals. Immunoreactive terminals contained numerous small clear vesicles and large dense core vesicles and formed synapses with unlabeled dendrites. In the nRVL, retrograde transport-immunofluorescence data demonstrated close appositions between vasopressinergic beaded processes and a compact subambigual column of reticulospinal neurons labeled by deposits of cholera toxin beta-subunit into the thoracic spinal cord. Similar methods were used to define the origins of the AVP-afferent projection to nRVL. These retrograde transport-immunofluorescence studies demonstrated numerous retrogradely labeled neurons in the hypothalamus, including the paraventricular nucleus (PVN), after injections of a retrograde tracer, Fluoro-Gold into the ventrolateral medulla. However, double-labeled neurons were rare and confirmed a diffuse AVP afferent innervation of the sympathoexcitatory area. Microinjection of AVP into the nRVL in anesthetized rats produced a large dose-related increase in AP different from control at a dose of 1 pmol or higher. AVP injected intravenously elevated AP only at significantly higher doses. Microinjections of AVP into the nucleus tractus solitarii (NTS) had a smaller effect whereas into the caudal ventrolateral medulla exerted no effect on AP. Bilateral microinjections of an AVP antagonist, d(CH2)5[Tyr(Me)2]AVP into the nRVL produced no change in AP but blocked the increase produced by subsequent injections of AVP. An acute hemorrhage produced by withdrawal of 2 ml of blood from the femoral vein did not alter AP. However, bilateral microinjections of the AVP antagonist into the nRVL 5 min after hemorrhage decreased AP. In contrast, the AVP-antagonist injected intravenously after hemorrhage had no effect on AP. Our data suggest that under conditions demanding increased sympathetic drive to maintain AP, such as hemorrhage, a functional AVP receptor mechanism via terminals in the nRVL may be activated to restore normal levels of AP.
Asunto(s)
Arginina Vasopresina/análisis , Presión Sanguínea , Encéfalo/fisiología , Bulbo Raquídeo/fisiología , Neuronas/fisiología , Animales , Arginina Vasopresina/administración & dosificación , Arginina Vasopresina/análogos & derivados , Arginina Vasopresina/farmacología , Arginina Vasopresina/fisiología , Transporte Axonal , Axones/fisiología , Axones/ultraestructura , Presión Sanguínea/efectos de los fármacos , Técnica del Anticuerpo Fluorescente , Hemorragia/fisiopatología , Masculino , Bulbo Raquídeo/citología , Bulbo Raquídeo/ultraestructura , Microinyecciones , Neuronas/citología , Neuronas/ultraestructura , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Sinapsis/fisiología , Sinapsis/ultraestructuraRESUMEN
The role of vasopressin (AVP) and angiotensin II (ANG II) in the onset of acute (45 min) aortic coarctation hypertension was studied in conscious rats. Changes in mean carotid pressure (MCP) and heart rate (HR) were measured in four groups of rats. Control rats presented a hypertensive response that attained a plateau 5 min after coarctation and remained near this level throughout the experiment. Rats treated with AVP V1-vascular receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]arginine vasopressin [d(CH2)5Tyr(Me)AVP] presented a prompt rise in MCP similar to the control rats, but in contrast to this group, the MCP started to decline progressively. Rats treated with saralasin presented a delay in the onset of hypertension right after coarctation but slowly attained values similar to those for control rats. In contrast, the rats treated with AVP antagonist plus saralasin showed a blunted MCP elevation throughout the experiment. Reflex bradycardia observed in the rats treated with saralasin or the AVP antagonist plus saralasin was similar to that observed in the control rats, whereas for the group treated only with AVP antagonist, the reflex bradycardia was more intense than for the other three groups, indicating an increased sensitivity of the baroreflex. These data demonstrate that in addition to the mechanical effect of aortic constriction, both ANG II and AVP participate in the onset of acute aortic coarctation hypertension. Moreover, the results indicate that ANG II acts on the prompt (5 min) rise in pressure, whereas AVP is responsible for the maintenance (30-45 min) of the arterial pressure elevation.
Asunto(s)
Angiotensina II/fisiología , Coartación Aórtica/complicaciones , Arginina Vasopresina/fisiología , Hipertensión/etiología , Enfermedad Aguda , Angiotensina II/antagonistas & inhibidores , Animales , Arginina Vasopresina/antagonistas & inhibidores , Arginina Vasopresina/farmacología , Presión Sanguínea/efectos de los fármacos , Arterias Carótidas/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión/fisiopatología , Masculino , Ratas , Ratas Endogámicas , Saralasina/farmacología , Vasopresinas/antagonistas & inhibidoresRESUMEN
The purpose of these studies was to assess the role of vasopressin in maintaining supine and upright blood pressures in hypertensive diabetic subjects. Patients with (n = 6) or without (n = 10) evidence of autonomic insufficiency had blood pressure and heart rate monitored before and after receiving an intravenous injection of 0.5 mg of a V1 vasopressin inhibitor. None of the patients had supine changes in blood pressure or heart rate. However, upon assuming the erect position, the six patients with preexisting orthostatic hypotension had an average blood pressure fall of 44 mm Hg after vasopressin inhibition (as opposed to 20 mm Hg before), accompanied by a modest rise in heart rate of 20 beats/min. Those without autonomic dysfunction were separated into two subgroups. Four developed an average fall in orthostatic blood pressure of 18 mm Hg after vasopressin inhibition, whereas the remaining six had no change. There were no distinguishing hormonal characteristics (vasopressin, renin, and catecholamine levels) between the groups, but in the patients with autonomic dysfunction, the renin level failed to rise when upright. We conclude that vasopressin plays an important role in preventing or minimizing orthostatic hypotension in diabetic patients. Its pressor contribution is crucial in those with autonomic insufficiency and impaired renin and sympathetic responses, in whom the pressor effectiveness of vasopressin is greatly enhanced.
Asunto(s)
Arginina Vasopresina/fisiología , Presión Sanguínea , Diabetes Mellitus Tipo 2/complicaciones , Hipotensión Ortostática/fisiopatología , Arginina Vasopresina/antagonistas & inhibidores , Femenino , Frecuencia Cardíaca , Humanos , Hipotensión Ortostática/etiología , MasculinoRESUMEN
1. The melanotropin-releasing activity of arginine-vasopressin (AVP), arginine-vasotocin (AVT), oxitocin (OT), mesotocin (MT) and corticotropin-releasing factor (CRF) was studied in the duck using dispersed, perfused pituitary cells and a specific alpha-MSH RIA. 2. Log dose-response curves were obtained for all the peptides ranging from 5 to 100 ng/ml. All peptides behaved as partial agonists compared to duck median eminence extracts (DME). 3. AVT and MT displayed an alpha-MSH releasing capacity of 60% relative to DME whereas all other peptides behaved as weak agonists with less than 15% capacity relative to DME. 4. AVT and CRF when perfused together acted synergistically on alpha-MSH release yielding a dose response line whose slope approximated that of DME. 5. ACTH was cosecreted together with alpha-MSH in all situations studied with an ACTH to alpha-MSH molar ratio of about 10. 6. It is concluded that CRF and neurohypophyseal peptides may be physiological stimulators of both alpha-MSH and ACTH release in aves.