Role of NO and K-ATP(+) channels in adenosine-induced vasodilation on in vivo canine subendocardial arterioles

Adenosine (Ado) plays an important role in regulation of coronary vascular tone with nitric oxide (NO) and ATP-sensitive K+ (K-ATP(+)) channels. In vi tro, it was reported that subendocardial (Endo) arterioles are more sensiti ve to Ado than subepicardial (Epi) arterioles. The purpose of this study wa s to observe enhanced vasodilation of Endo arterioles directly and to evalu ate possible roles of K-ATP(+) channels and NO in the different responses o f Endo and Epi arterioles to Ado-induced vasodilation. We evaluated dilatio n of Endo and Epi arterioles (<120 mu m) of beating canine hearts (n = 19) by Ado (20 and 50 mu g.kg(-1) min(-1) ic) before and after K-ATP(+) channel blockade (glibenclamide; 200 mu g/kg ic), inhibition of NO synthase [N-G-n itro-L-arginine methyl ester (L-NAME); 30 mu g kg(-1) min(-1), 20 min ic] o r glibenclamide + L-NAME using a novel needle-probe CCD intravital microsco pe. Ado induced dose-dependent vasodilation in both Epi and Endo arterioles , but vasodilation was greater in Endo arterioles, i.e., increase at 120 s (maximum dilation) after Ado (50 mu g.kg(-1) min-1) was 17% in Endo and 13% in Epi arterioles (P < 0.01). Endo arteriole dilation was attenuated by bl ockade of K-ATP(+), channels from 18% (Ado) to 9% (Ado + glibenclamide) inc rease (P < 0.001) and by inhibition of NO synthase from 17% (Ado) to 9% (Ad o+L-NAME) (P < 0.005). Epi arteriole vasodilation was attenuated by blockad e of K-ATP(+) channels from 15 to 9% (P < 0.005) and inhibition of NO from 16 to 10% (P < 0.005). Suppression of vascular response was additive (Endo, 14 to -1%; Epi, 12 to 3%) with glibenclamide + L-NAME. We conclude that 1) the degree of Ado-induced vasodilation was greater in Endo than in Epi art erioles, with higher sensitivity of smaller arterioles in both layers and 2 ) transmural difference of arteriolar sensitivity to adenosine;was abolishe d or reversed by K-ATP(+) channel blockade and/or by NO synthase inhibition , indicating crucial involvement of K-ATP(+) and NO in transmural sensitivi ty difference.