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

Léna Borbouse, Gregory M. Dick, Gregory A. Payne, Brittany D. Payne, Mark C. Svendsen, Zachary P. Neeb, Mouhamad Alloosh, Ian N. Bratz, Michael Sturek, Johnathan D. Tune

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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 (MV̇O2). 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 μg/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 MV̇O2 (P < 0.001) that was accompanied by a marked release of lactate (negative lactate uptake) as MV̇O2 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 MV̇O2 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.

Original languageEnglish (US)
Pages (from-to)H966-H973
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume298
Issue number3
DOIs
StatePublished - Mar 2010

Keywords

  • Coronary blood flow
  • Exercise
  • Myocardial oxygen consumption
  • Ossabaw miniature swine
  • Penitrem A

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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