Contribution of BKCa channels to local metabolic coronary vasodilation: effects of metabolic syndrome

Contribution of BKCa channels to local metabolic coronary vasodilation: effects of metabolic syndrome

Borbouse L; Dick G M; Payne G A; Payne B D; Svendsen M C; Neeb Z P; Alloosh M; Bratz I N; Sturek M; Tune J D

American Journal of Physiology-Heart and Circulatory Physiology

2010

2010-03

Borbouse L, Dick GM, Payne GA, Payne BD, Svendsen MC, Neeb ZP, Alloosh M, Bratz IN, Sturek M, Tune JD. Contribution of BKCa channels to local metabolic coronary vasodilation: effects of metabolic syndrome. Am J Physiol Heart Circ Physiol 298: H966-H973, 2010. First published December 31, 2009; doi:10.1152/ajpheart.00876.2009.-This investigation was designed to examine the hypothesis that impaired function of coronary microvascular large-conductance Ca2+-activated K+ (BKCa) channels in metabolic syndrome (MetS) significantly attenuates the balance between myocardial oxygen delivery and metabolism at rest and during exercise-induced increases in myocardial oxygen consumption (M(V) over dotO(2)). Studies were conducted in conscious, chronically instrumented Ossabaw swine fed a normal maintenance diet (11% kcal from fat) or an excess calorie atherogenic diet (43% kcal from fat, 2% cholesterol, 20% kcal from fructose) that induces many common features of MetS. Data were collected under baseline/resting conditions and during graded treadmill exercise before and after selective blockade of BKCa channels with penitrem A (10 mu g/kg iv). We found that the exercise-induced increases in blood pressure were significantly elevated in MetS swine. No differences in baseline cardiac function or heart rate were noted. Induction of MetS produced a parallel downward shift in the relationship between coronary venous PO2 and M(V) over dotO(2) (P < 0.001) that was accompanied by a marked release of lactate (negative lactate uptake) as M(V) over dotO(2) was increased with exercise (P < 0.005). Inhibition of BKCa channels with penitrem A did not significantly affect blood pressure, heart rate, or the relationship between coronary venous PO2 and M(V) over dotO(2) in lean or MetS swine. These data indicate that BKCa channels are not required for local metabolic control of coronary blood flow under physiological (lean) or pathophysiological (MetS) conditions. Therefore, diminished function of BKCa channels does not contribute to the impairment of myocardial oxygen-supply demand balance in MetS.

exercise; Physiology; Cardiovascular System & Cardiology; nitric-oxide; blood flow; coronary blood flow; smooth-muscle-cells; insulin-resistance; cardiovascular-disease; pigs; ca2+-activated k+ channels; induced relaxation; Ossabaw miniature swine; A; diabetic dyslipidemic; exercising dogs; myocardial oxygen consumption; myocardial-metabolism; penitrem

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H966-H973

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