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

Division of Experimental Cardiology, Department of Cardiology, Thoraxcenter, Cardiovascular Research School COEUR, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands

Submitted 28 March 2006 ; accepted in final form 10 May 2006

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 O₂ delivery increased commensurately with the increase in myocardial O₂ consumption, so that myocardial O₂ extraction and coronary venous PO₂ () were maintained constant. TEA (in a dose that had no effect on K_ATP⁺ channels) had a small effect on the myocardial O₂ balance at rest and blunted the exercise-induced increase in myocardial O₂ delivery, resulting in a progressive decrease of with increasing exercise intensity. Conversely, at rest glibenclamide caused a marked decrease in 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.

coronary circulation; calcium-activated potassium channels; adenosine 5'-triphosphate-sensitive potassium channels

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