KCa+ channels contribute to exercise-induced coronary vasodilation in swine

Coronary blood flow is controlled via several vasoactive mediators that exert their effect on coronary resistance vessel tone through activation of K+ channels in vascular smooth muscle. Because Ca2+-activated K+ (K-Ca(+)) channels are the predominant K+ channels in the coronary vasculature, we hypothesized that K-Ca(+) channel activation contributes to exercise-induced coronary vasodilation. In view of previous observations that ATP-sensitive K+ (K-ATP(+)) channels contribute, in particular, to resting coronary resistance vessel tone, we additionally investigated the integrated control of coronary tone by K-Ca(+) and K-ATP(+) channels. For this purpose, the effect of K-Ca(+) blockade with tetraethylammonium (TEA, 20 mg/kg iv) on coronary vasomotor tone was assessed in the absence and presence of K-ATP(+) channel blockade with glibenclamide (3 mg/kg iv) in chronically instrumented swine at rest and during treadmill exercise. During exercise, myocardial O-2 delivery increased commensurately with the increase in myocardial O-2 consumption, so that myocardial O-2 extraction and coronary venous PO2 (Pcv(O2)) were maintained constant. TEA (in a dose that had no effect on K-ATP(+) channels) had a small effect on the myocardial O-2 balance at rest and blunted the exercise-induced increase in myocardial O-2 delivery, resulting in a progressive decrease of Pcv(O2) with increasing exercise intensity. Conversely, at rest glibenclamide caused a marked decrease in Pcv(O2) that waned at higher exercise levels. Combined K-Ca(+) and K-ATP(+) channel blockade resulted in coronary vasoconstriction at rest that was similar to that caused by glibenclamide alone and that was maintained during exercise, suggesting that K-Ca(+) and K-ATP(+) channels act in a linear additive fashion. In conclusion, K-Ca(+) channel activation contributes to the metabolic coronary vasodilation that occurs during exercise. Furthermore, in swine K-Ca(+) and K-ATP(+) channels contribute to coronary resistance vessel control in a linear additive fashion.