ADENOSINE POTENTIATES FLOW-INDUCED DILATION OF CORONARY ARTERIOLES BY ACTIVATING K-ATP CHANNELS IN ENDOTHELIUM

Coronary microvascular diameter is significantly influenced by adenosine and flow. However, the interaction between these two regulatory mechanisms in the control of coronary microvascular tone remains unknown. Because adenosine can activate ATP-sensitive K+ (K-ATP) channels and these channels are located on the endothelium in addition to vascular smooth muscle, we hypothesized that adenosine can potentiate flow-induced vasodilation by activating endothelial K-ATP channels in the coronary microcirculation. To test this hypothesis, experiments were performed in porcine subepicardial coronary arterioles (50-150 mu m) using isolated, cannulated vessel techniques to allow intraluminal pressure and flow to be independently controlled. All vessels developed active tone, similar to 67-73% of maximum diameter, at 60 cmH(2)O intraluminal pressure and showed graded dilation to stepwise increases in flow. The magnitude of flow-induced dilation was potentiated by a threshold dose of adenosine (10(-10) M) but not by nitroprusside (10(-10) M). Luminal application of a high K+ concentration ([(K+)]) (40 mM) completely blocked flow-induced arteriolar dilation. In addition, luminal glibenclamide (10(-6) M) abolished the adenosine-potentiated component of flow-induced response. Indomethacin (10(-5) M) did not alter the dose-dependent dilation to adenosine. However, endothelial denudation, N-G-monomethyl-L-arginine (10(-5) M), and luminal administration of a high [K+] or glibenclamide each produced identical inhibition of adenosine-induced vasodilation by shifting the 50% effective dose to the right by an order of magnitude. In constrast, vasodilation in response to nitroprusside was not altered by these pharmacological interventions. Based on these results, we conclude that coronary arteriolar dilation in response to adenosine is partially mediated by the endothelial release of nitric oxide (NO) via the opening of K-ATP channels. Our findings are consistent with the hypothesis that adenosine potentiates flow-induced vasodilation by activating endothelial K-ATP channels. We speculate that activation of endothelial K-ATP channels may enhance increases in intracellular [Ca2+] for NO synthesis and thus potentiate vasodilation in response to flow.