Relaxant Actions of α2-Adrenoceptor Agonists in Rat Aorta |
In-gook Cho1, Sang-woo Lee1, Hyung-sub Kang1, Heyng-seok Seo2, Jin-shang Kim1 |
1Bio-Safety Research Institute, Chonbuk National University 2Chonbuk Livestock and Veterinary Research Institute |
α2-Adrenoceptor Agonists의 흰쥐 대동맥 이완 작용 |
조인국1, 이상우1, 강형섭1, 서형석2, 김진상1 |
1전북대학교 생체안전성연구소 2 |
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Abstract |
The vasorelaxant actions and blood pressure lowering of the ${alpha}_2$-adrenoceptor agonists (${alpha}_2$-AAs) clonidine and xylazine were investigated in rat isolated aortic rings and anesthesized rats. Both clonidine and xylazine produced a concentration-dependent inhibition of the sustained contraction induced by norepinephrine (NE), but not by KCl. NE-induced contractions were attenuated partly by nifedipine or verapamil, voltage dependent $Ca^{2+}$ channel blockers. These $Ca^{2+}$ channel blockers-resistant contractions were abolished by clonidine or xylazine. Inhibitory effects of a ${alpha}_2$-AAs on contractions could be reversed by ryanodine, an intracellular $Ca^{2+}$, transport blocker, and tetrabutylammonium (TBA), a $Ca^{2+}$ activated $K^+$ channel blocker, but not by nifedipine, glibenclamide or removal of extracellular $Ca^{2+}$ and endothelium. Moreover, ${alpha}_2$-AAs produced relaxation in NE-precontracted isolated intact aortic rings in a concentration-dependent manner, but not in KCl-precontracted rings. The relaxant effects of ${alpha}_2$-AAs were inhibited by ryanodine and TBA, but not by nifedipine, glibenclamide, N (G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG), 2-nitro-4-carboxyphenyl N,N-diphenylcarhurnte (NCDC), lithium sulfate, staurosporine or removal of extracellular $Ca^{2+}$ and endothelium. In vivo, infusion of xylazine elicited significant decrease in anerial blood pressure. This xylazinelowered blood pressure was completely inhibited by the intravenous injection of TBA, but not by the intravenous injection of glibenclamide, L-NNA, L-NAME, AG, nifedipine, lithium sulfate or saponin.. These findings showed that the receptor-mediated and ${alpha}_2$-adrenoceptor A-stimulated endothelium-independent vasorelaxant effect may be explained by decreasing intracellular $Ca^{2+}$ release and activation of $Ca^{2+}$-activated $K^+$ channels, which may contribute to the hypotensive effects of ${alpha}_2$-AAs in rats. |
Key Words:
${alpha}_2$-adrenoceptor agonists, vasorelaxant effect, blood pressure, ryanodine, aorta |
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