RESUMO
We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT2R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT2R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca2+-free medium or the subsequent tonic constrictions induced by the addition of Ca2+ in the absence of agonists. Thus, the contractions induced by Ca2+ release from intracellular stores and Ca2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca2+. Neither levels of angiotensins nor of AT2R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca2+ entry.
Assuntos
Animais , Masculino , Aorta Torácica/fisiopatologia , Coartação Aórtica/fisiopatologia , Cálcio/metabolismo , Endotélio Vascular/fisiologia , Músculo Liso Vascular/fisiopatologia , Proteína Quinase C/antagonistas & inibidores , Vasoconstrição/fisiologia , Angiotensina I/análise , Angiotensina II/análise , Aorta Torácica/lesões , Aorta Torácica/cirurgia , Western Blotting , Pressão Sanguínea/fisiologia , Cromatografia Líquida de Alta Pressão , Endotélio Vascular/lesões , Músculo Liso Vascular/metabolismo , Fármacos Neuromusculares Despolarizantes/farmacologia , Fenilefrina/farmacologia , Potássio/farmacologia , Proteína Quinase C/metabolismo , Radioimunoensaio , Ratos Wistar , /metabolismo , Vasoconstrição/efeitos dos fármacosRESUMO
We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT2R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT2R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca2+-free medium or the subsequent tonic constrictions induced by the addition of Ca2+ in the absence of agonists. Thus, the contractions induced by Ca2+ release from intracellular stores and Ca2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca2+. Neither levels of angiotensins nor of AT2R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca2+ entry.
Assuntos
Aorta Torácica/fisiopatologia , Coartação Aórtica/fisiopatologia , Cálcio/metabolismo , Endotélio Vascular/fisiologia , Músculo Liso Vascular/fisiopatologia , Proteína Quinase C/antagonistas & inibidores , Vasoconstrição/fisiologia , Angiotensina I/análise , Angiotensina II/análise , Animais , Aorta Torácica/lesões , Aorta Torácica/cirurgia , Pressão Sanguínea/fisiologia , Western Blotting , Cromatografia Líquida de Alta Pressão , Endotélio Vascular/lesões , Masculino , Músculo Liso Vascular/metabolismo , Fármacos Neuromusculares Despolarizantes/farmacologia , Fenilefrina/farmacologia , Potássio/farmacologia , Proteína Quinase C/metabolismo , Radioimunoensaio , Ratos Wistar , Receptor Tipo 2 de Angiotensina/metabolismo , Vasoconstrição/efeitos dos fármacosRESUMO
To evaluate the relationship between the vasocontractile effect of thiopental and the extra and intracellular sources of Ca2+, we analyzed both the contractile effect of the barbiturate on rat aortic rings and its ability to modify the intracellular calcium concentration in cultured rat aorta smooth muscle cells. Thiopental (10-310 microg/mL) contracted aortic rings only in the presence of extracellular Ca2+, and this effect was not blocked by verapamil or diltiazem. On the contrary, Ca2+ (0.1-3.1 mM) evoked contractions only when thiopental (100 microg/mL) was present. Although in calcium-free solution thiopental (100 microg/mL) did not contract aortic rings, it abolished the contractile effect of either phenylephrine (10(-6) M) or caffeine (10 mM). Finally, thiopental augmented the intracellular calcium concentration in cultured smooth muscle cells incubated either in the presence or absence of calcium. In conclusion, thiopental's vasocontractile effect depends on extracellular calcium influx, which is independent of L-calcium channels. The increase in intracellular Ca2+ concentration elicited by thiopental in Ca2+-free solution and its ability to block the effect of phenylephrine and caffeine suggest that this barbiturate can deplete intracellular pools of calcium. Therefore, the calcium entry pathway associated with the contractile effect of thiopental may correspond to the capacitative calcium entry model.
Assuntos
Cálcio/metabolismo , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Tiopental/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Aorta , Cafeína/farmacologia , Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Diltiazem/farmacologia , Endotélio Vascular/fisiologia , Hipnóticos e Sedativos/farmacologia , Técnicas In Vitro , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Fenilefrina/farmacologia , Ratos , Ratos Wistar , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia , Verapamil/farmacologiaAssuntos
Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico , Óxido Nítrico/biossíntese , Tiopental/farmacologia , Acetilcolina/farmacologia , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Histamina/farmacologia , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacologia , Nitritos/metabolismo , Ratos , Ratos WistarAssuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Diclofenaco/farmacologia , Atividade Motora/efeitos dos fármacos , Dor/complicações , Animais , Cafeína/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Masculino , Ratos , Ratos Wistar , Fatores de Tempo , Ácido Úrico/efeitos adversosAssuntos
Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Artérias Umbilicais/efeitos dos fármacos , Veias Umbilicais/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Humanos , Indometacina/farmacologia , Recém-Nascido , NG-Nitroarginina Metil Éster/farmacologia , Nitroprussiato/farmacologia , Técnicas de Cultura de Órgãos , Serotonina/farmacologia , Vasoconstrição/efeitos dos fármacosRESUMO
The subtype(t) of alpha-adrenoceptor-mediating contractions to alpha-methynoradrenaline in the rat aorta has been investigated by using alpha-adrenoceptor-selective competitive antagonists and the alpha 1-adrenoceptor selective agonist, phenylephrine, for comparison. alpha-Methylnoradrenaline and phenylephrine elicited concentration-dependent contractions in the endothelium-denuded and endothelium-intact aortic rings with similar potencies and maximal effects. alpha-Methylnoradrenaline- and phenylephrine-induced contractions in endothelium-denuded aortic rings were competitively antagonized by prazosin (pA2 = 9.38 and 9.13; respectively) and rauwolscine (pA2 = 7.19 and 6.60, respectively). This confirms that there is an alpha 1- and a non alpha 2-adrenoceptor response to alpha-methylnoradrenaline in the rat aorta. The subtype selective alpha 1D-adrenoceptor antagonist, BMY 7378, was found to antagonize contractions to alpha-methylnoradrenaline and phenylephrine competitively in endothelium-denuded and endothelium-intact aortic rings. The pA2 values of BMY 7378 against alpha-methylnoradrenaline (8.39 and 8.41; endothelium-intact and endothelium-denuded, respectively) and phenylephrine (8.64 and 8.76; endothelium-intact and endothelium-denuded, respectively), are consistent with its published functional potency and clonal alpha 1D-adrenoceptor binding affinity. In addition, contractions to alpha-methylnoradrenaline and phenylephrine in endothelium-denuded aortic rings, were potently inhibited by WB 4101 with pA2 values of 9.75 and 9.25, respectively. The high pA2 values for WB 4101 indicate that the alpha 1B-adrenoceptor subtype does not seem to participate in alpha-methylnoradrenaline (and phenylephrine) induced contractions in this artery. These results suggest that the alpha 1D-subtype plays a determining role in rat aorta contractions induced by alpha-methylnoradrenaline.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Aorta/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Nordefrin/farmacologia , Fenilefrina/farmacologia , Vasoconstritores/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Aorta/química , Aorta/fisiologia , Interações Medicamentosas , Endotélio Vascular/química , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Masculino , Contração Muscular/fisiologia , Ratos , Ratos WistarRESUMO
The aim of this study was to determine if like buspirone, ipsapirone and 8-hydroxy-2(di-N-propylamino)tetralin (8-OH-DPAT), the alpha 1-adrenoceptors are involved in the responses elicited by indorenate in rabbit aorta. Exception made of ipsapirone, all the 5-HT1A agonists above mentioned contracted aortic rings. The contraction elicited by buspirone and 8-OH-DPAT was blocked with prazosin (alpha 1-adrenergic antagonist), whereas the effect of indorenate was unaffected with this blocker but it was inhibited with ritanserin (5-HT2 antagonist). On the other hand, buspirone, ipsapirone and 8-OH-DPAT but not indorenate relaxed arteries precontracted with methoxamine (alpha 1-adrenergic agonist) and none of the agonists relaxed preparations precontracted with acetylcholine or KCl. The results indicate that buspirone and 8-OH-DPAT are partial alpha 1-adrenoceptor agonists since they elicited contractions which are blocked with prazosin and relaxed only rings precontracted with methoxamine. Ipsapirone behaved as an alpha 1-adrenoceptor antagonist since it showed the relaxant but not the contractile effect. Finally, we found no evidence that indorenate has afinity for alpha 1-adrenoceptors. Contraction elicited by this agonist seems to be mediated by 5-HT2 receptors, inasmuch it was blocked with ritanserin.