ROLE OF K+(ATP) CHANNELS IN CORONARY VASODILATION DURING EXERCISE

Background. The mechanism of metabolic regulation of coronary vascular tone is still unclear. Therefore, we examined the role of vascular sm ooth muscle K+ATP channels in regulating coronary blood flow under res ting conditions, during increments in myocardial metabolic demand prod uced by treadmill exercise, and in response to a brief ischemic stimul us. Methods and Results. Ten chronically instrumented dogs were studie d at rest and during a four-stage exercise protocol under control cond itions and during intracoronary infusion of the K+ATP channel blocker glybenclamide at rates of 10 and 50 mug . kg-1 . min-1. Glybenclamide (50 mug . kg-1 . min-1) decreased coronary blood flow at rest from 51/-4 to 42+/-6 mL/min (P<.05), decreased myocardial oxygen consumption from 5.70+/-0.31 to 4.11+/-0.56 mL O2/min (P<.05), and decreased systo lic wall thickening from 21+/-3% to 12+/-3% (P<.05). The depression of systolic wall thickening produced by glybenclamide was reversed when coronary blood flow was restored to the control level with intracorona ry nitroprusside, indicating a primary effect of glybenclamide on coro nary flow during resting conditions. However, glybenclamide did not im pair the increases of coronary blood flow, myocardial oxygen consumpti on, and systolic wall thickening that occurred during exercise. In eig ht resting awake dogs, 50 mug . kg-1 . min-1 glybenclamide decreased t he peak reactive hyperemia blood flow rate following a 20-second coron ary occlusion from 149+/-14 mL/min during control conditions to 111+/- 15 mL/min (P<.05), decreased the duration of reactive hyperemia from 4 9+/-6 to 33+/-3 seconds (P<.05), and decreased reactive hyperemia exce ss flow from 33+/-5 to 20+/-4 mL (P<.05). Conclusions. These data demo nstrate that K+ATP channels modulate coronary vasomotor tone under res ting conditions and contribute to coronary vasodilation during ischemi a. However, the coronary vasculature retains the capacity to dilate in response to increases in oxygen demand produced by exercise when K+AT P channels are blocked.