title: Contribution of BK(Ca) channels to local metabolic coronary vasodilation: Effects of metabolic syndrome.
abstract: This investigation was designed to examine the hypothesis that impaired function of coronary microvascular large-conductance Ca(2+)-activated K(+) (BK(Ca)) 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 (MVo(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 BK(Ca) channels with penitrem A (10 microg/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 Po(2) and MVo(2) (P < 0.001) that was accompanied by a marked release of lactate (negative lactate uptake) as MVo(2) was increased with exercise (P < 0.005). Inhibition of BK(Ca) channels with penitrem A did not significantly affect blood pressure, heart rate, or the relationship between coronary venous Po(2) and MVo(2) in lean or MetS swine. These data indicate that BK(Ca) channels are not required for local metabolic control of coronary blood flow under physiological (lean) or pathophysiological (MetS) conditions. Therefore, diminished function of BK(Ca) channels does not contribute to the impairment of myocardial oxygen-supply demand balance in MetS.
authors.affiliation: Dept. of Cellular and Integrative Physiology, Indiana Univ. School of Medicine, Indianapolis, 46202, USA.
authors.forename: Léna
authors.initials: L
authors.lastname: Borbouse
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Dick
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Payne
authors.forename: Brittany D
authors.initials: BD
authors.lastname: Payne
authors.forename: Mark C
authors.initials: MC
authors.lastname: Svendsen
authors.forename: Zachary P
authors.initials: ZP
authors.lastname: Neeb
authors.forename: Mouhamad
authors.initials: M
authors.lastname: Alloosh
authors.forename: Ian N
authors.initials: IN
authors.lastname: Bratz
authors.forename: Michael
authors.initials: M
authors.lastname: Sturek
authors.forename: Johnathan D
authors.initials: JD
authors.lastname: Tune
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000503:physiopathology*; D004195:Disease Models, Animal; D006339:Heart Rate / Q000502:physiology; D024821:Metabolic Syndrome / Q000503:physiopathology*; D009183:Mycotoxins / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology; D013552:Swine; D014664:Vasodilation / Q000502:physiology*
chemical_list: D009183:Mycotoxins; D024681:Potassium Channels, Calcium-Activated; C003626:tremortin