Adenosine potentiates flow-induced dilation of coronary arterioles by activating atp-sensitive potassium channels in endothelium. Kuo, Lih, and Jeff D. Chancellor. Department of Medical Physiology, Microcirculation Research Institute, Texas A&M University Health Science Center, College Station, TX 77843-1114
APStracts 2:0071H, 1995.
The diameter of coronary resistance vessels can be significantly influenced by adenosine and flow. However, the interaction between these two regulatory mechanisms in the control of coronary microvascular tone remains unknown. Since adenosine can activate ATP -sensitive potassium (KATP) channels and these channels are located on endothelium in addition to vascular smooth muscle, we hypothesized that adenosine can potentiate flow-induced vasodilation by activating endothelial KATP 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. Flow-induced dilation was studied in the presence and absence of a threshold dose of adenosine (10-10 M) or nitroprusside (10-10 M). The involvement of endothelial KATP channels and nitric oxide in adenosine-induced responses were evaluated by using specific inhibitors, i.e., glibenclamide and NG-monomethyl-L -arginine (L-NMMA), respectively, before and after endothelial removal. All vessels developed a similar level of active tone (67-73% of maximum diameter) at 60 cmH2O intraluminal pressure and showed graded dilation to stepwise increases in flow. The highest flow produced the dilation to reach 86% of maximum diameter. The magnitude of flow-induced dilation was potentiated (97% of maximum diameter) by adenosine but not by nitroprusside. Lumenal application of high potassium (40 mM) completely blocked arteriolar dilation in response to the increased flow. In addition, lumenal 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, L-NMMA (10-5 M), or lumenal administration of high potassium or glibenclamide each produced identical inhibition of adenosine-induced vasodilation by shifting the adenosine ED50 to the right by an order of magnitude (from 6x10-8 to 6x10-7 M). In contrast, 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 via the opening of KATP channels. Our findings are consistent with the hypothesis that adenosine potentiates flow-induced vasodilation by activating endothelial KATP channels. We speculate that activation of endothelial KATP channels may enhance increases in intracellular calcium for nitric oxide synthesis and thus potentiate vasodilation in response to flow. 

Received 15 December 1994; accepted in final form 28 February
1995.
APS Manuscript Number H1098-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.