Vasorelaxant effects of glibenclamide on rat thoracic aorta: sıçan torasik aortasında glibenklamidin vazorelaksan etkileri

Abstract

The purpose of this study was to investigate the effect of glibenclamide, a selective ATP-sensitive K+(KATP) channel blocker, on agonist-induced contractions in isolated rat aortic rings. The possible involvement of endothelium in glibenclamide-induced response was also investigated. The concentrationresponse curves of prostaglandin F2α (PGF2α; 0.1 nM-30 µM), serotonin (5-hydroxytryptamine, 5-HT; 1 nM30 µM) and phenylephrine (1 nM-30 µM) were obtained in the absence or presence of glibenclamide (1, 3 or 10 µM). Maximum agonist-induced contractions in the presence of glibenclamide 1, 3 and 10 µM were decreased by 30±5, 64±3 and 86±2 percent for PGF2αand 41±11, 50±11 and 65±5 percent for 5-HT respectively. Phenylephrine-induced contractions remained unaltered by glibenclamide 10 µM. The inhibitory effect of glibenclamide (10 µM) on PGF2α- or 5-HT-induced contractions were attenuated upon Nω-nitro-L-arginin (L-NNA; 100 µM) plus indomethacin (10 µM) incubation. The inhibitory effect of glibenclamide on PGF2α-induced contractions was also assessed in endothelium-denuded arteries and the inhibitory effect of glibenclamide was greater in endothelium-denuded arteries than in endothelium-intact arteries pretreated with L-NNA plus indomethacin (64±4% versus 46±10%, respectively). These results suggest that glibenclamide could act through multiple sites in either endothelium or the underlying arterial smooth muscle and thus serve as a non-selective muscle relaxant at high concentration