GLIBENCLAMIDE, A SPECIFIC INHIBITOR OF ATP-SENSITIVE K-II RECEPTOR ANTAGONISTS( CHANNELS, INHIBITS CORONARY VASODILATION INDUCED BY ANGIOTENSIN)

The purpose of our study was test the hypothesis that endogenous angio tensin II contributes to the basal coronary artery tone by acting at v ascular ATP-sensitive K+ (K(+)ATP) channels. Coronary blood flow (CBF) and other hemodynamic parameters were measured in anesthetized dogs. Intracoronary infusion of the selective antagonists of angiotensin II AT(1) receptors (L-158,809 and E4177) increased CBF without affecting other hemodynamic parameters, indicating that endogenous angiotensin I I caused coronary vasoconstriction through the AT(1) subtype receptors . Coronary vasodilation in response to AT(1) receptor antagonists was blunted by pretreatment with glibenclamide (a specific inhibitor of K( +)ATP channels; p < 0.01) but not by either an adenosine-receptor anta gonist or an inhibitor of nitric oxide synthesis. Coronary vasodilatio n in response to AT(1)-receptor antagonists was partly reduced (p < 0. 01) by PD-123319 (the AT(2)-receptor antagonist). Glibenclamide had no effect on coronary vasodilation induced by sodium nitroprusside. Thes e results indicate that in dogs in vivo, coronary vasodilation in resp onse to AT(1)-receptor antagonists inhibited markedly by glibenclamide and partly by PD-123319, suggesting that endogenous angiotensin II co ntributes to the maintenance of basal coronary vascular tone by acting at K(+)ATP channels through its receptors.