Abstract 1142: Voltage-Dependent K+ Channels Mediate Coronary Vasodilation in Response to Ischemia and Adenosine
Reactive hyperemia, the transient increase in blood flow following a brief period of ischemia, is attributed to vasodilator metabolites such as adenosine. Mechanisms of ischemia- and adenosine-induced coronary vasodilation are incompletely understood, but may involve specific K+ channels in vascular smooth muscle. We tested the hypothesis that voltage-dependent K+ (KV) channels mediate vasodilation in response to ischemia and adenosine. Responses to 30 second interruptions in blood flow were measured in open-chest dogs before and after inhibition of KV channels with 4-aminopyridine (4-AP). Hyperemic flow (area under the curve until blood flow returned to baseline) was 37 ± 7 ml under control conditions. Intracoronary 4-AP (0.3 mM in the plasma) reduced baseline flow 33 ± 4% (p < 0.05) and inhibited hypermic flow to 19 ± 5 ml (n = 7; p < 0.05). Intracoronary adenosine increased blood flow in dose-dependent manner and this was attenuated by 0.3 mM 4-AP (64 ± 13 vs. 27 ± 9 ml/min increase at 9 μg/min; n = 4; p < 0.05). Adenosine dilated coronary arterioles, cannulated and pressurized to 60 mmHg, in a concentration-dependent manner and this was attenuated by 0.3 mM 4-AP (63 ± 5 vs. 21 ± 6% dilation at 10 μm; n = 5; p < 0.05). Patch clamp experiments revealed that 10 μM adenosine increased KV current 63 ± 7% at −20 mV (n = 4; p < 0.05) and hyperpolarized membrane potential 12 ± 3 mV (n = 4; p < 0.05). Our data indicate that KV channels play a critical role in ischemia- and adenosine-induced coronary vasodilation through the regulation of microvascular smooth muscle membrane potential.