Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation

Borbouse L, Dick GM, Payne GA, Berwick ZC, Neeb ZP, Alloosh M, Bratz IN, Sturek M, Tune JD. Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation. Am J Physiol Heart Circ Physiol 298: H1182-H1189, 2010. First published January 29, 2010; doi: 10.1152/ajpheart.00888.2009.-This investigation tested the hypothesis that metabolic syndrome decreases the relative contribution of specific K+ channels to coronary reactive hyperemia. Ca2+-activated (BKCa), voltage-activated (K-V), and ATP-dependent (K-ATP) K+ channels were investigated. Studies were conducted in anesthetized miniature 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) for 20 wk. The latter diet induces metabolic syndrome, increasing body weight, fasting glucose, total cholesterol, and triglyceride levels. Ischemic vasodilation was determined by the coronary flow response to a 15-s occlusion before and after cumulative administration of antagonists for BKCa (penitrem A; 10 mu g/kg iv), K-V (4-aminopyridine; 0.3 mg/kg iv) and K-ATP (glibenclamide; 1 mg/kg iv) channels. Coronary reactive hyperemia was diminished by metabolic syndrome as the repayment of flow debt was reduced similar to 30% compared with lean swine. Inhibition of BKCa channels had no effect on reactive hyperemia in either lean or metabolic syndrome swine. Subsequent inhibition of KV channels significantly reduced the repayment of flow debt (similar to 25%) in both lean and metabolic syndrome swine. Additional blockade of K-ATP channels further diminished (similar to 45%) the repayment of flow debt in lean but not metabolic syndrome swine. These data indicate that the metabolic syndrome impairs coronary vasodilation in response to cardiac ischemia via reductions in the contribution of K+ channels to reactive hyperemia.