915-76 ATP-sensitive Potassium Channels Contribute to Reactive Hyperemia in Humans

Abstract

Activation of ATP-sensitive potassium channels (KATP) of vascular smooth muscle causes hyperpolarization of the cell membrane and vasodilation. The purposes of this study were 1) to determine whether KATP contribute to reactive hyperemia following ischemia in humans, and 2) whether adenosine, a metabolite present in ischemic muscle, activates KATP. Accordingly, we studied the effect of tolbutamide (1 mM), a KATP inhibitor, on reactive hyperemic forearm blood flow in 12 normal subjects. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Forearm ischemia was produced by inflating a blood pressure cuff to suprasystolic pressures for 5 minutes. Following cuff release FBF was measured during the reactive hyperemic phase for 5 minutes. After a re-equilibration period the above protocol was repeated during intra-brachial artery infusion of either tolbutamide 1 mM (n = 6) or vehicle (n = 6). Blood flow was plotted vs. time and the area under the curve was calculated after subtracting baseline flow. Tolbutamide did not significantly alter basal FBF (2.5 ± 0.6 to 2.3 ± 1.0 ml/100 ml/min), or peak reactive hyperemic FBF (21.9 ± 9.2 to 22.6 ± 7.2 ml/100 ml/min) (each p = ns). However, tolbutamide significantly attenuated total hyperemic flow repayment; (156 ± 44 vs. 114 ± 32 ml/100 ml, p = 0.02). Vehicle did not impair basal flow, peak reactive hyperemic flow or repayment. Tolbutamide 1 mM did not attenuate adenosine-induced(15-500 mM) increases in FBF (n = 6). These data indicate that KATP contribute to vasodilation during reactive hyperemia in humans. Activation of KATP is not mediated by adenosine.