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 vitro, it was reported that subendocardial (Endo) arterioles are more sensitive to Ado than subepicardial (Epi) arterioles. The purpose of this study was to observe enhanced vasodilation of Endo arterioles directly and to evaluate possible roles of K(+)(ATP) channels and NO in the different responses of Endo and Epi arterioles to Ado-induced vasodilation. We evaluated dilation of Endo and Epi arterioles (<120 micrometer) of beating canine hearts (n = 19) by Ado (20 and 50 microgram. kg(-1). min(-1) ic) before and after K(+)(ATP) channel blockade (glibenclamide; 200 microgram/kg ic), inhibition of NO synthase [N(G)-nitro-L-arginine methyl ester (L-NAME); 30 microgram. kg(-1). min(-1), 20 min ic], or glibenclamide + L-NAME using a novel needle-probe CCD intravital microscope. 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 microgram. kg(-1). min(-1)) was 17% in Endo and 13% in Epi arterioles (P < 0.01). Endo arteriole dilation was attenuated by blockade of K(+)(ATP) channels from 18% (Ado) to 9% (Ado+glibenclamide) increase (P < 0.001) and by inhibition of NO synthase from 17% (Ado) to 9% (Ado+L-NAME) (P < 0.005). Epi arteriole vasodilation was attenuated by blockade 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 arterioles, with higher sensitivity of smaller arterioles in both layers and 2) transmural difference of arteriolar sensitivity to adenosine was abolished or reversed by K(+)(ATP) channel blockade and/or by NO synthase inhibition, indicating crucial involvement of K(+)(ATP) and NO in transmural sensitivity difference.