RESUMO
It is shown that 3-(3-[1,2,4]-triazolo)-oxatriazolium-5-olate (azasidnon-6) can act directly on the vascular wall of isolated segments of caudal ventral artery of SHR rats. Using heme-dependent soluble guanyl cyclase inhibitor 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), it has been found that one of the possible mechanisms of azasidnon-6 vasodilatory action includes heme-dependent activation of a soluble form of guanylate cyclase.
Assuntos
Artérias/efeitos dos fármacos , Triazóis/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Guanilato Ciclase/antagonistas & inibidores , Guanilato Ciclase/metabolismo , Heme/metabolismo , Masculino , Óxido Nítrico/metabolismo , Nitroprussiato/farmacologia , Oxidiazóis/farmacologia , Fenilefrina/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Cauda/irrigação sanguínea , Técnicas de Cultura de Tecidos , Vasoconstritores/farmacologiaRESUMO
Long-term peroral administration of the oxatriazolo-5-olate derivative azasydnon-6 leads to a decrease in the systolic arterial blood pressure in SHR rats. The hypotensive effect of azasydnon-6 is mediated by stimulation of the sGC-cGMP pathway, which triggers vasodilatation of SMC in vessels. The drug effect is inhibited by 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one, a selective sGC inhibitor. During long-term treatment, no tolerance to azasydnon-6 is developed in isolated arterial vessels.
Assuntos
Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Triazóis/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Anti-Hipertensivos/administração & dosagem , GMP Cíclico/antagonistas & inibidores , Guanilato Ciclase/antagonistas & inibidores , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Oxidiazóis/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Endogâmicos SHR , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Guanilil Ciclase SolúvelRESUMO
Intravenous administration of azasidnon-6 (oxatriazolium-5-olate derivative) induces prolonged dose-dependent decrease in arterial blood pressure in awake Wistar and SHR rats. Hypotensive effects of azasidnon-6 in SHR rats is significantly higher during inhibition of endogenous NO synthesis.
