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+ (KCa + ) channels are the predominant K+ channels in the coronary vasculature, we hypothesized that KCa + channel activation contributes to exercise-induced coronary vasodilation. In view of previous observations that ATPsensitive K+ (KATP + ) channels contribute, in particular, to resting coronary resistance vessel tone, we additionally investigated the integrated control of coronary tone by KCa + and KATP + channels. For this purpose, the effect of KCa + blockade with tetraethylammonium (TEA, 20 mg/kg iv) on coronary vasomotor tone was assessed in the absence and presence of KATP + channel blockade with glibenclamide (3 mg/kg iv) in chronically instrumented swine at rest and during treadmill exercise. During exercise, myocardial O2 delivery increased commensurately with the increase in myocardial O2 consumption, so that myocardial O 2 extraction and coronary venous PO2 (PcvO2) 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 O2 delivery, resulting in a progressive decrease of PcvO2 with increasing exercise intensity. Conversely, at rest glibenclamide caused a marked decrease in PcvO2 that waned at higher exercise levels. Combined KCa + and KATP + 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 KCa + and K ATP + channels act in a linear additive fashion. In conclusion, KCa + channel activation contributes to the metabolic coronary vasodilation that occurs during exercise. Furthermore, in swine KCa + and KATP + channels contribute to coronary resistance vessel control in a linear additive fashion. Copyright

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