Role of large conductance Ca2+‐activated K+ (BKCa) channels in local metabolic coronary vasodilation in Ossabaw swine with metabolic syndrome

Abstract

This study examined the contribution of BKCa channels to local metabolic coronary vasodilation in Ossabaw swine fed a normal maintenance diet (lean) or excess atherogenic diet that induces metabolic syndrome (MetS). Coronary blood flow responses during graded exercise were measured in conscious, chronically‐instrumented swine before and after specific BKCa antagonism with penitrem A (10 μg/kg, iv) that significantly decreased coronary vasodilation to the BKCa agonist NS1619. MetS developed over 20 weeks as evidenced by elevated body weight 51%, arterial pressure 13% and plasma insulin 80% without affecting fasting glucose. The relationship between coronary venous PO2 (cvPO2) and myocardial O2 consumption (MVO2) was significantly decreased in MetS relative to lean. This impaired balance between coronary blood flow and myocardial metabolism was accompanied by a negative lactate uptake during exercise in MetS (−1.8 ± 1.3 μmol/min/g), but not in lean (1.7 ± 0.6 μmol/min/g) swine (P < 0.01). BKCa inhibition did not significantly affect arterial pressure, heart rate or diminish the cvPO2‐MVO2 relationship in either lean or MetS swine. These findings indicate that BKCa channels are not required for coronary vasodilation to exercise and that the imbalance between myocardial O2 delivery and metabolism in MetS is not related to altered functional expression of BKCa channels. (Support: HL67804, RR013223, HL062552)