RESUMO

Several reports have demonstrated that depressive disorder is related to somatic symptoms including gastrointestinal or genitourinary alterations. The pathophysiological mechanisms underlying the gastrointestinal or genitourinary alterations associated with the depression are still not fully understood. Therefore, this study aimed to evaluate the motor activity of gastrointestinal (fundus of stomach and duodenum) and genitourinary tract (bladder) in a stress-based animal model of depression. Adult male mice were submitted to uncontrollable and unpredictable stress (learned helplessness model), controllable stress and non-stressful situations (control). Then, animals were euthanized and the fundus of stomach, duodenum segments or whole bladder were isolated and mounted in a standard organ bath preparation. We evaluated the contractile effects induced by KCl 80 mM for 5 min or carbachol (acetylcholine receptor agonist). The relaxant effects of isoproterenol (ß-adrenoceptor agonist) were also checked. Animals submitted to the learned helplessness model developed a helpless (depressive-like behavior) or resilient (does not exhibit depressive-like behavior) phenotype. The contractions induced by carbachol were diminished in fundus of stomach isolated from helpless and resilient animals. The isoproterenol-induced fundus of stomach relaxation was reduced in resilient but not helpless mice. The contractions/relaxation of duodenum segments isolated from helpless or resilient animals were not altered. Both helpless and resilient animals showed an increase in the bladder contractions induced by carbachol while the relaxant effects of isoproterenol were reduced when compared to control. Conversely, mice underwent a controllable stress situation did not exhibit alterations in the fundus of stomach or duodenum contraction/relaxation induced by pharmacological agents although a decrease in the bladder contraction induced by carbachol was found. In conclusion, incontrollable and unpredictable stress and not depressive phenotype (helpless animals) or controllable stress could be related to the alterations in motor activity of the fundus of stomach and bladder.

Assuntos

Depressão , Bexiga Urinária , Camundongos , Masculino , Animais , Carbacol/farmacologia , Isoproterenol/farmacologia , Estômago/fisiologia , Contração Muscular/fisiologia , Duodeno

Assuntos

COVID-19 , Homeopatia , Humanos , Método Duplo-Cego , Preparações Farmacêuticas , Resultado do Tratamento

RESUMO

The motor activity of the epididymis duct is an essential process for male fertility and it is regulated by hormonal, neuronal and epithelial mechanisms. However, although there is evidence for the presence of histamine in the epididymis, its effects on epididymal motor activity are unknown. This study sought to evaluate the contractile effects of histamine on the rat distal cauda epididymis duct. Segments of the distal cauda epididymis duct from male Wistar rats were isolated and used in isolated organ bath experiments to evaluate the contractile effects of histamine in the absence or presence of antagonists of histamine receptors, α1-adrenoceptors and muscarinic acetylcholine receptors. The effects of histamine on noradrenaline induced contractions were also investigated. Histamine was able to induce phasic contractions on rat distal cauda epididymis duct which were prevented by promethazine 10-1000 nM (H1 receptor antagonist), ranitidine 1-100 µM (H2 receptor antagonist), atropine 100 nM (muscarinic antagonist), and prazosin 100 nM (α1-adrenoceptor antagonist). In addition, histamine was also able to modify noradrenaline-induced contractions possibly via activation of H1 and H2 receptors. In conclusion, this study demonstrates that histamine can induce phasic contractions of rat distal cauda epididymis via H2 receptors and autonomic neurotransmitters. Histamine may also exert modulatory actions on contractions of rat distal cauda epididymis duct induced by adrenergic receptor agonists. Further studies are necessary to unveil the localization of histamine receptors within the epididymal duct and the consequences of manipulation of the histaminergic system on epididymal function and male fertility.

Assuntos

Epididimo , Histamina , Ratos , Masculino , Animais , Ratos Wistar , Histamina/farmacologia , Prazosina/farmacologia , Norepinefrina/farmacologia , Receptores Adrenérgicos alfa 1

RESUMO

The effects of dipyrone and acetylsalicylic acid (ASA) on male fertility are still not fully understood, mainly considering the epididymis as a putative target for their anti-fertility effects. Therefore, this study aimed to investigate the effects of dipyrone and ASA on the contractions of distal cauda epididymis duct, serum testosterone levels and sperm parameters in rats. Firstly, we checked the in vitro effects of dipyrone and ASA (10-1000 µM) on the contractions of distal cauda epididymis duct by pharmacological experiments. We also evaluated the effects of in vivo treatment with dipyrone and ASA 100 mg/kg (p.o.) for 15 days on epididymal duct contractions, serum testosterone levels and sperm parameters. In vitro dipyrone or ASA decreased the epididymal duct contractions induced by phenylephrine or carbachol. We observed that in vivo treatment with both drugs decreased the daily sperm production, serum testosterone levels and sperm count through epididymis without altering the epididymal duct contractions and sperm transit time through epididymis. In conclusion, in vitro dipyrone and ASA were able to diminish the contractions of epididymal duct, whilst in vivo administration decreased the sperm count throughout epididymis as a consequence of a low sperm production caused by reduced testosterone levels.

Assuntos

Epididimo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Aspirina , Dipirona , Epididimo/fisiologia , Genitália/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Contagem de Espermatozoides , Testosterona/sangue , Testosterona/metabolismo

RESUMO

The testicular capsules of different mammalian species exhibit spontaneous motor activity. In addition, contractions can be mediated by neuronal stimulation or exogenous drug administration. However, the physiological role of testicular capsule motor activity is still not well understood. Nevertheless, there is evidence for putative roles in spermatozoa transport from the testis to the caput epididymis, control of interstitial/intratesticular pressure and testicular blood flow. In this review, we have collated information about the agents that regulate testicular capsule motor activity, their receptors and second messengers as well as the impact of altered testicular capsule function on the male reproductive system. Furthermore, we highlight the knowledge gaps in the physiology and pharmacology of the testicular capsule as indicators of future research directions that may lead to a better understanding of the physiological role of testicular capsule motor activity and its importance in male fertility.

Assuntos

Sistema Nervoso Autônomo/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/inervação , Animais , Sistema Nervoso Autônomo/fisiologia , Fertilidade/efeitos dos fármacos , Humanos , Masculino , Pressão , Fluxo Sanguíneo Regional , Motilidade dos Espermatozoides/efeitos dos fármacos

RESUMO

Fluoxetine and sertraline are antidepressants drugs capable to impair male fertility by decreasing the number of sperm cells in the ejaculate. However, the mechanism underlying these effects is still not fully understood. It is also reported that alterations in epididymis contraction induced by different drugs affect the number of sperm cells, leading to male fertility alterations. Therefore, this study aimed to investigate if both fluoxetine and sertraline could affect the rat epididymis contraction, altering the sperm transit and/or sperm count trough rat epididymis. In vitro effects of fluoxetine and sertraline (1, 3 and 10 µM) were evaluated in isolated distal cauda epididymis of rats by pharmacological experiments. The effects of long-term treatment with fluoxetine and sertraline (20 mg/kg, i.p., 21 days) were also checked on distal cauda epididymis contractions, serum testosterone levels, sperm production, sperm reserves and sperm transit time trough rat epididymis. In vitro fluoxetine and sertraline (>3 µM) impaired the contractions induced by KCl, phenylephrine or carbachol although fluoxetine 1 µM potentiate the phenylephrine-induced contractions. Long-term in vivo treatment with fluoxetine and sertraline promoted: (a) an enhancement of rat distal cauda spontaneous contractions; (b) a potentiation of phenylephrine-induced contractions; (c) a decreased in serum testosterone levels; and (d) a diminished daily sperm production, sperm reserves trough epididymis and sperm transit time in rat cauda epididymis. In conclusion, the alteration in the motor activity of epididymis could be associated to the low sperm count in this organ and accelerated transit time trough epididymal cauda of rats.

Assuntos

Antidepressivos/farmacologia , Epididimo/efeitos dos fármacos , Fluoxetina/farmacologia , Sertralina/farmacologia , Espermatozoides/efeitos dos fármacos , Animais , Epididimo/fisiologia , Masculino , Ratos Wistar , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia

RESUMO

Hypertension represents an autonomic dysfunction, characterized by increased sympathetic and decreased parasympathetic cardiovascular tone leading to resting tachycardia. Therefore, studies assessing hypertension-associated changes in isolated cardiac tissues were conducted under electric field stimulation to stimulate the neurons. Herein, we characterize the influence of the autonomic neurotransmitter on the baseline atrial chronotropism of unpaced isolated right atria of normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR). Our results revealed a resting bradycardia in tissues from SHR in comparison to NWR. The release of autonomic neurotransmitters, acetylcholine or norepinephrine, still occurs in the electrically unstimulated right atrium, after excision of the sympathetic nerve, which could explain differences in basal heart rate between NWR and SHR. Nicotine and the acetylcholinesterase inhibitor physostigmine reduced the chronotropism of right atria from either NWR or SHR. Conversely, the muscarinic receptor antagonist atropine did not affect the basal chronotropism of tissues from both strains. Furthermore, tyramine increased the chronotropism of NWR and SHR atria indicating availability of the neuronal stocks of noradrenaline. Although the monoamine uptake inhibitor cocaine increased right atrium chronotropism in both strains, the basal heart rate was not affected by the ß-adrenoceptor antagonist propranolol. In summary, after acute section of the sympathetic nerve, autonomic neurotransmitters are still released either in resting conditions or upon pharmacological stimulation of right atria from both strains. Nevertheless, autonomic neurotransmission does not affect resting chronotropism, nor is the responsible for reduced basal heart rate of the isolated right atrium of hypertensive rats.

Assuntos

Função do Átrio Direito , Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea , Bradicardia/fisiopatologia , Átrios do Coração/inervação , Frequência Cardíaca , Hipertensão/fisiopatologia , Acetilcolina/metabolismo , Adaptação Fisiológica , Animais , Função do Átrio Direito/efeitos dos fármacos , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/metabolismo , Bradicardia/diagnóstico , Bradicardia/etiologia , Modelos Animais de Doenças , Estimulação Elétrica , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/complicações , Hipertensão/diagnóstico , Masculino , Neurotransmissores/farmacologia , Norepinefrina/metabolismo , Ratos Endogâmicos SHR , Ratos Wistar , Fatores de Tempo

RESUMO

In the right atrium (RA), adenosine and acetylcholine inhibit the pacemaker function of the sinoatrial node and induce cardiac arrest. Pre-incubation of receptor antagonists is known to inhibit the cardiac arrest induced by these agonists; however, the effect of antagonist administration after established cardiac arrest has not been described. Therefore, we assessed whether specific receptor antagonists could revert cardiac arrest induced by adenosine and muscarinic receptors activation. RA isolated from adults Wistar rats were mounted in an organ bath containing Krebs solution. Cardiac arrest was induced by adenosine or ATP (1mM), the A1 adenosine receptor agonist CPA (0.1-1µM), and muscarinic receptor agonists, carbachol (0.3-1µM) and acetylcholine (1mM). After establishing the cardiac arrest, the A1 adenosine receptor antagonist DPCPX (0.3-30µM), the muscarinic receptor antagonist atropine (10nM to 100µM) or the phosphodiesterase inhibitor IBMX (10-300µM) were incubated in order to check for the return of spontaneous contractions. DPCPX reversed the cardiac arrest induced by adenosine, ATP and CPA. In addition, atropine reversed the cardiac arrest induced by carbachol. Unexpectedly, DPCPX also reversed the cardiac arrest induced by carbachol. Similarly to DPCPX, the phosphodiesterase inhibitor IBMX reversed the cardiac arrest induced by adenosine, CPA and carbachol. The antagonism of adenosine and acetylcholine receptors activation, as well as phosphodiesterase inhibition, are able to revert cardiac arrest. DPCPX restore spontaneous contractions via the selective antagonism of A1 adenosine receptor and through a secondary mechanism likely related to phosphodiesterase inhibition.

Assuntos

Agonistas do Receptor A1 de Adenosina/farmacologia , Parada Cardíaca/induzido quimicamente , Parada Cardíaca/tratamento farmacológico , Agonistas Muscarínicos/farmacologia , Receptor A1 de Adenosina/metabolismo , Receptores Muscarínicos/metabolismo , Xantinas/farmacologia , Animais , Carbacol/farmacologia , Masculino , Ratos , Ratos Wistar , Xantinas/uso terapêutico

RESUMO

Schinus terebinthifolius Raddi (Anacardiaceae), popularly known as red aroeira, is used in traditional medicine to treat inflammatory, gastric, and respiratory disorders. The aim of this study was to evaluate the antihistaminic activity of S. terebinthifolius (St) bark extract by using in vivo and in vitro experimental models. The effects of St were investigated on contractions induced by histamine, carbachol, and potassium chloride in isolated guinea pig ileum. St was also studied in response to hind paw edema induced by histamine in rats. Experiments revealed that although St (250, 500, and 1,000 µg/mL) reduced the histamine-induced contractions by 9.1 ± 1.8, 50.2 ± 2.0, and 68.9 ± 2.0%, respectively, it did not inhibit contractions induced by carbachol or KCl. The association of St (250 and 500 µg/mL) with hydroxyzine, an H1-antihistamine (0.125 and 0.250 µM), increased the inhibitory effect to 67.0 ± 3.2 and 85.1 ± 2.1%, respectively. Moreover, St (100, 200, and 400 mg/kg) decreased paw edema from its peak by 33.9, 48.4, and 54.8%, respectively, whereas hydroxyzine (70 mg/kg) inhibited the peak edema by 56.5%. Altogether, the results suggest that the bark extract of S. terebinthifolius has an antihistaminic effect (H1).

RESUMO

It is described that fluoxetine treatment is able to induce ejaculatory disorders. However, the exact mechanism is still not fully understood. Therefore, this study was carried out to further evaluate the anti-ejaculatory effects of fluoxetine, using different approaches (in vitro or in vivo treatments), on the sympathetic neurotransmission of the rat vas deferens. Vas deferens from male Wistar rats were used to check the in vitro effects of fluoxetine 10-6M, 3.10-6M or 10-5M. Animals were also acutely (20mg/kg, i.p. 4h or 24h) or chronically (10mg/kg, i.p., 30days) treated with fluoxetine or drug-free vehicle. The vas deferens from non-treated and treated animals were isolated and mounted in an isolated organ bath for the study of the contractions induced by adrenergic agonists, tyramine, 5-HT, Ca2+ or electrical field stimulation. In vitro or acute treatment with fluoxetine decreased the contraction induced by agonists, Ca2+ or electrical field stimulation. The chronic treatment with fluoxetine decreased the contractions induced agonists, tyramine or Ca2+, but did not modify the contractions induced by electrical field stimulation. We have shown that in vitro or in vivo fluoxetine treatment is able to alter the sympathetic neurotransmission of the rat vas deferens which could be related to alterations in the calcium signalling.

Assuntos

Fluoxetina/administração & dosagem , Simpatolíticos/administração & dosagem , Transmissão Sináptica/efeitos dos fármacos , Ducto Deferente/efeitos dos fármacos , Animais , Cálcio/metabolismo , Avaliação Pré-Clínica de Medicamentos , Ejaculação/efeitos dos fármacos , Ejaculação/fisiologia , Masculino , Ratos Wistar , Simpatomiméticos/farmacologia , Transmissão Sináptica/fisiologia , Fatores de Tempo , Técnicas de Cultura de Tecidos , Ducto Deferente/fisiologia

RESUMO

Autonomic nerves release ATP, which is processed into adenosine in the synaptic cleft. Adenosine and ATP exert a negative chronotropic effect in the heart. This study aims to evaluate adenosine and P2 receptors and cellular signalling in cardiac arrest produced by purines in the heart. Right atria of adult Wistar rats were used to evaluate the effects of adenosine, ATP and CPA (an adenosine A1 receptor agonist), in the presence and absence of DPCPX, an adenosine A1 receptor antagonist. Effects of adenosine A2 and A3 receptors agonists and antagonists were also investigated. Finally, involvement of calcium and potassium channels in these responses was assessed using BayK 8644 and 4-Aminopyridine. Cumulative concentration-effect curves of adenosine and CPA resulted in a negative chronotropic effect culminating in cardiac arrest at 1000µM (adenosine) and 1µM (CPA). Furthermore, ATP produced a negative chronotropic effect at 1-300µM and cardiac arrest at 1000µM in the right atrium. ATPγS (a non-hydrolysable analogue of ATP) reduced chronotropism only. The effects of adenosine, CPA and ATP were inhibited by DPCPX, a selective adenosine A1 receptor antagonist. The selective adenosine A2 and A3 receptors antagonists did not alter the chronotropic response of adenosine. 4-Aminopyridine, a blocker of potassium channels at 10mM, prevented the cardiac arrest produced by adenosine and ATP, while BayK 8644, activator of calcium channels, did not prevent cardiac arrest. Adenosine A1 receptor activation by adenosine and ATP produces cardiac arrest in the right atrium of Wistar rats predominantly through activation of potassium channels.

Assuntos

Trifosfato de Adenosina/farmacologia , Adenosina/farmacologia , Canais de Cálcio/metabolismo , Parada Cardíaca/induzido quimicamente , Parada Cardíaca/metabolismo , Átrios do Coração/efeitos dos fármacos , Canais de Potássio/metabolismo , Animais , Relação Dose-Resposta a Droga , Parada Cardíaca/patologia , Parada Cardíaca/fisiopatologia , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Agonistas do Receptor Purinérgico P1/farmacologia , Ratos , Ratos Wistar , Receptores Purinérgicos P1/metabolismo

RESUMO

AIMS: Testicular capsule contractile dysfunctions are recognized to contribute to male infertility, but the influence of sexual maturation and exogenous testosterone on the expression and function of androgen receptor and α1-adrenoceptors on rat testicular capsule is unclear. Here, these two biological parameters were evaluated on testicular capsule from sexually immature and young adult rats treated or not with exogenous testosterone. MAIN METHODS: Male Wistar rats (45- and 60-day-old) were assigned into groups: control (saline 0.9%) or testosterone-treated (propionate testosterone). Testicular capsule was isolated and processed for functional studies, immunohistochemistry, Western blot and RT-PCR studies. KEY FINDINGS: Relative testicular capsule wet weight was not affected by sexual maturation or exogenous testosterone treatment. The expression and immunolocalization of androgen receptor (mRNA and protein) was identified in testicular capsule. Androgen receptor and α1-adrenoceptor (Adra1a, Adra1b, and Adra1d) mRNA levels were similar in testicular capsule from all experimental groups. Functional studies indicated that contractions produced by noradrenaline in testicular capsule from 45- and 60-day-old rats treated or not with testosterone were mainly mediated by α1A- and α1B-adrenoceptors. The L-type Ca(2+) channel blocker nifedipine induced a higher inhibitory effect on noradrenaline induced contractions in testicular capsule from 45- than 60-day-old rats treated with testosterone. SIGNIFICANCE: Molecular studies, immunohistochemistry and pharmacological functional assays used in this study provide evidences of the androgen receptor expression in testicular capsule and that function, and not mRNA and protein expression levels of the α1-adrenoceptor subtypes in this tissue, is differentially influenced by the rat androgen status.

Assuntos

Receptores Adrenérgicos alfa 1/fisiologia , Receptores Androgênicos/biossíntese , Receptores Androgênicos/fisiologia , Maturidade Sexual/fisiologia , Testículo/fisiologia , Testosterona/fisiologia , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Nifedipino/farmacologia , Norepinefrina/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/fisiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Wistar , Receptores Adrenérgicos alfa 1/biossíntese , Testículo/crescimento & desenvolvimento , Testículo/metabolismo , Testosterona/farmacologia

RESUMO

Histamine is an important modulatory agent of the sympathetic neurotransmission, but its exact action on the testicular capsule or rat vas deferens is not fully understood. The present study sought to further investigate the functional effects of histamine on the neuronal and exogenous noradrenaline-induced contraction of the testicular capsule and rat vas deferens as well as to evaluate the contractile properties of this drug. The testicular capsule or vas deferens from Wistar rats, 3-4 months old, weighing 300-400 g, was isolated and mounted in organ baths for functional experiments. The results indicated that the neuronally evoked contraction of the testicular capsule was affected by histamine (10(-10) to 10(-8) M) with participation of inhibitory (H3 receptors) and excitatory (H1 receptors) receptors. Histamine (10(-7) to 10(-4) M) modulated the field-stimulated vas deferens by excitatory (H2 receptors) and inhibitory (H1 receptors) receptors. Histamine was able to decrease the tonic response for noradrenaline-induced contractions with participation of H1 receptors (testicular capsule) and H3 receptors (vas deferens) followed by nitric oxide generation. At high concentration, histamine exerts contractile effects in both tissues. In the testicular capsule, the histamine-induced contractions were related to H1 receptor activation followed by release of prostaglandins. In contrast, the contractile effects of histamine in the vas deferens were related to H2 receptor activation followed by release of catecholamines from sympathetic nerve endings. Therefore, our results indicate that histamine induced several effects on the sympathetic neurotransmission of rat testicular capsule and vas deferens. These effects are dependent on the concentration used and with participation of multiple histamine receptors.

Assuntos

Histamina/farmacologia , Testículo/efeitos dos fármacos , Ducto Deferente/efeitos dos fármacos , Animais , Estimulação Elétrica , Técnicas In Vitro , Masculino , Óxido Nítrico/fisiologia , Norepinefrina/farmacologia , Ratos Wistar , Receptores Histamínicos/fisiologia , Sistema Nervoso Simpático/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Testículo/fisiologia , Ducto Deferente/fisiologia

RESUMO

The motor activity of mammalian testicular capsule (TC) contributes to male fertility and infertility, but the acetylcholine receptors related to the contractions induced by cholinergic drugs are poorly known. Indeed to characterize the acetylcholine receptors and cellular signaling by Ca(2+) involved in TC motor activity of rats, the potency of agonists (pD2) and antagonists (pA2) of acetylcholine receptors, and effects of Ca(2+) cellular transport blockers on the cholinergic contractions were evaluated. pD2 values of acetylcholine (5.98) were ten-fold higher than that of carbachol (4.99). Efficacy (Emax) of acetylcholine and carbachol to induce contractions corresponded to 95% and 97% of Emax for KCl, but Emax for nicotine was very low (8% of Emax for KCl). Further, physostigmine did not affect the acetylcholine potency. Contractions induced by acetylcholine or carbachol were antagonized by muscarinic but not nicotinic antagonist. The order of pA2 values obtained for muscarinic antagonists, namely atropine>4-DAMP>AF-DX116>pirenzepine, corresponded to a typical profile of M3 receptors. Contractions induced by acetylcholine or carbachol were inhibited by blockers of Ca(2+) influx through voltage-dependent calcium channels (nifedipine and Ni(2+)), Ca(2+) reuptake by sarco-endoplasmic reticulum (cyclopiazonic acid) and mitochondria (FCCP). The protein kinase C (PKC) inhibitor chelerythrine only affected the acetylcholine-induced contraction. These results suggest that TC motor activity of rats are mediated mainly by M3 receptors followed by the increase of cytosolic Ca(2+) concentration regulated by voltage-dependent calcium channels, sarco-endoplasmic reticulum and mitochondria. Furthermore, the differential effects of chelerythrine in the acetylcholine or carbachol-induced contractions are discussed.

Assuntos

Sinalização do Cálcio , Receptores Colinérgicos/metabolismo , Testículo/citologia , Testículo/metabolismo , Acetilcolina/farmacologia , Animais , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Carbacol/farmacologia , Agonistas Colinérgicos/farmacologia , Antagonistas Colinérgicos/farmacologia , Relação Dose-Resposta a Droga , Técnicas In Vitro , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Masculino , Contração Muscular/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores Muscarínicos/metabolismo , Testículo/efeitos dos fármacos , Testículo/fisiologia

RESUMO

From experiments performed at room temperature, we know that the buffering of Ca(2+) by mitochondria contributes to the shaping of the bulk cytosolic calcium transient ([Ca(2+)]c) and secretion transients of chromaffin cells stimulated with depolarizing pulses. We also know that the mitochondrial Ca(2+) transporters and the release of catecholamine are faster at 37°C with respect to room temperature. Therefore, we planned this investigation to gain further insight into the contribution of mitochondrial Ca(2+) buffering to the shaping of [Ca(2+)]c and catecholamine release transients, using some novel experimental conditions that have not been yet explored namely: (1) perifusion of bovine chromaffin cells (BCCs) with saline at 37°C and their repeated challenging with the physiological neurotransmitter acetylcholine (ACh); (2) separate blockade of mitochondrial Ca(2+) uniporter (mCUP) with Ru360 or the mitochondrial Na(+)/Ca(2+) exchanger (mNCX) with CGP37157; (3) full blockade of the mitochondrial Ca(2+) cycling (mCC) by the simultaneous inhibition of the mCUP and the mNCX. Ru360 caused a pronounced delay of [Ca(2+)]c clearance and augmented secretion. In contrast, CGP37157 only caused a tiny delay of [Ca(2+)]c clearance and a mild decrease in secretion. The mCC resulting in continued Ca(2+) uptake and its release back into the cytosol was interrupted by combined Ru360 + CGP37157 (Ru/CGP), the protonophore carbonyl cyanide-p-trifluoromethoxyphenylhydrazone, or combined oligomycin + rotenone (O/R); these three treatments caused a mild but sustained elevation of basal [Ca(2+)]c that, however, was not accompanied by a parallel increase in basal secretion. Nevertheless, all treatments caused a pronounced augmentation of ACh-induced secretion, with minor changes of the ACh-induced [Ca(2+)]c transients. Combined Ru/CGP did not alter the resting membrane potential in current-clamped cells. Additionally, Ru/CGP did not increase basal [Ca(2+)]c near subplasmalemmal sites and caused a mild decrease in the size of the readily releasable vesicle pool. Our results provide new functional features in support of the view that in BCCs there are two subpopulations of mitochondria, M1 underneath the plasmalemma nearby exocytotic sites and M2 at the core cell nearby vesicle transport sites. While M1 serves to shape the ACh-elicited exocytotic response through its efficient Ca(2+) removal by the mCUP, M2 shapes the lower [Ca(2+)]c elevations required for new vesicle supply to the exocytotic machinery, from the large reserve vesicle pool at the cell core. The mCUP of the M1 pool seems to play a more prominent role in controlling the ACh responses, in comparison with the mNCX.

RESUMO

Previous studies conducted in our laboratory indicated that administration of amphetamine, fluoxetine or sibutramine affects the sympathetic nervous system of the rat vas deferens. Therefore, our goal was to verify the role of calcium in vasa deferentia from young rats pretreated with a single dose of these drugs. Young 40-day-old male Wistar rats were pretreated with amphetamine 3 mg/kg, fluoxetine 10 mg/kg or sibutramine 6 mg/kg for 4 h before the experiments. CaCl(2) (10 mM) was used to induce contraction through time-effect curves in calcium-free solution to measure phasic and tonic components. We also evaluated the calcium-induced fluorescence of vas deferens cut into thin slices. In rats pretreated with amphetamine, we found an increase of the tonic contraction component which was reduced by verapamil. The phasic and tonic responses were increased in the group treated with fluoxetine, but only the tonic response was more sensitive to the antagonism by verapamil. The group treated with sibutramine showed an increase of phasic response whereas the tonic component was decreased. In this group an increase of the affinity for verapamil antagonism was found. In the calcium fluorescence study it was observed that the group treated with amphetamine, fluoxetine or sibutramine showed higher basal Ca(2+) fluorescence after stimulus with KCl (70 mM), noradrenaline (10(-4)M) or acetylcholine (10(-4)M). In all pretreated groups the calcium fluorescence was diminished by nifedipine 10(-7)M. Therefore, the pretreatment with amphetamine, fluoxetine or sibutramine seems to affect the calcium contractility and homeostasis in young rat vas deferens.

Assuntos

Cálcio/metabolismo , Fármacos do Sistema Nervoso Central/farmacologia , Citosol/efeitos dos fármacos , Citosol/metabolismo , Contração Muscular/efeitos dos fármacos , Ducto Deferente/citologia , Ducto Deferente/fisiologia , Anfetamina/farmacologia , Animais , Ciclobutanos/farmacologia , Fluoxetina/farmacologia , Homeostase/efeitos dos fármacos , Técnicas In Vitro , Masculino , Músculo Liso/citologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Ratos , Ratos Wistar , Fatores de Tempo , Ducto Deferente/efeitos dos fármacos

RESUMO

Because of the few studies that emphasize the in vivo use of amphetamine and ethanol, and their consequences on autonomic neurotransmission, we decided to study the effect of these drugs on peripheral noradrenergic neurotransmission of young animals. We used contractions of the vas deferens of adolescent rats as a model for the study of pre-treatment with both agents. The 30 to 40 day old adolescent rats were pre-treated with amphetamine, at doses of 3mg/kg, or ethanol at doses of 1.2 g/kg. Both agents were also used simultaneously to investigate possible interactions. The group treated with amphetamine showed a potentiation of the vas deferens contractions evoked by noradrenaline and barium (about 20%), as well as time-response contractions of calcium (about 20%). However, the response to electrical field stimulation (EFS) was not significantly changed, but the content of noradrenaline was reduced by about 50%. The group treated with ethanol showed a decrease in vas deferens contractility to noradrenaline, phenylephrine, and barium, by less than 20%. In this group, contraction by EFS was reduced by about 40% (Tonic, 2 Hz) and 20% (Phasic, 5 Hz), but the response to calcium was not changed. As after amphetamine, the content of noradrenaline was reduced by about 50%. In the group treated with amphetamine+ethanol all the changes described after the single treatments with amphetamine or ethanol were neutralized. It is concluded that a functional antagonism was shown between amphetamine and ethanol when administered simultaneously on peripheral sympathetic neurotransmission in vas deferens of adolescent animals.

Assuntos

Neurônios Adrenérgicos/citologia , Neurônios Adrenérgicos/efeitos dos fármacos , Anfetamina/farmacologia , Etanol/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Ducto Deferente/citologia , Neurônios Adrenérgicos/metabolismo , Animais , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Estimulação Elétrica , Masculino , Músculo Liso/inervação , Norepinefrina/metabolismo , Ratos , Ratos Wistar , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Fatores de Tempo , Ducto Deferente/efeitos dos fármacos , Ducto Deferente/metabolismo , Ducto Deferente/fisiologia

RESUMO

A infecção do trato urinário (ITU) constitui uma das patologias mais prevalentes no mundo e responde por grande parte dos processos infecciosos.O trabalho objetivou avaliar a frequência de isolamento das bactérias, analisando a faixa etária, g~enero mais acometido e avaliar o perfil de resistência aos antimicrobianos. O estudo caracterizou-se por uma pesquisa histórico documental, na qual foram analisadas 1957 uroculturas realizadas no Laboratório de Análises Clínicas - HEMOCLIN na cidade de Campina Grande - PB no período de janeiro de 2006 a junho de 2008...Pode-se concluir que o diagnóstico correto da ITUse torna importante, permitindo a aplicação de um tratamento adequado evitando o uso indiscriminado de antimicrobianos.

Assuntos

Humanos , Masculino , Feminino , Resistência Microbiana a Medicamentos , Infecções por Escherichia coli , Pacientes Ambulatoriais , Prevalência , Infecções Urinárias

RESUMO

Uma das questões de relevância para a Farmacovigilância é a detecção/identificação de interações medicamentosas. Muitas das reações adversas a medicamentos (RAMs) são causadas por interações medicamentosas. Há numerosos estudos que têm como enfoque as RAMs dos antiinflamatórios não-esteróides (AINEs) sobre a pressão arterial e a diminuição da eficácia dos medicamentos anti-hipertensivos. Assim, o estudo teve por objetivo identificar as possíveis interações entre AINEs e anti-hipertensivos, detectar as principais RAMs ocasionadas por tais medicamentos e o possível impacto na pressão arterial. Trata-se de um estudo descritivo e exploratório realizado mediante uma abordagem transversal e qualiquantitativa em pacientes hipertensos internados na clínica geral de um hospital público. Dos 47 participantes, mais da metade eram homens; houve grande porcentagem de idosos. A interação mais frequente foi entre a dipirona e o captopril. Constatou-se que metade dos pacientes apresentaram a média dos níveis pressóricos acima de 139/89 mmHg; a outra metade relatou possíveis RAMs relacionadas com a elevação dos níveis pressóricos. É possível, por meio da Farmacovigilância, detectar tais interações e promover discussões na equipe de saúde com intuito de melhorar a farmacoterapia dos pacientes assistidos em qualquer hospital público do país.

Assuntos

Humanos , Masculino , Idoso , Anti-Hipertensivos , Coleta de Dados , Hipertensão/terapia , Preparações Farmacêuticas/efeitos adversos , Pesquisa Qualitativa