Exercise training normalizes beta-adrenoceptor expression in dogs susceptible to ventricular fibrillation

Am J Physiol Heart Circ Physiol. 2007 Nov;293(5):H2702-9. doi: 10.1152/ajpheart.00763.2007. Epub 2007 Aug 24.

Abstract

Previous studies demonstrated an enhanced beta(2)-adrenoceptor (AR) responsiveness in animals susceptible to ventricular fibrillation (VF) that was eliminated by exercise training. The present study investigated the effects of endurance exercise training on beta(1)-AR and beta(2)-AR expression in dogs susceptible to VF. Myocardial ischemia was induced by a 2-min occlusion of the left circumflex artery during the last minute of exercise in dogs with healed infarctions: 20 had VF [susceptible (S)] and 13 did not [resistant (R)]. These dogs were randomly assigned to either 10-wk exercise training [treadmill running; n = 9 (S) or 8 (R)] or an equivalent sedentary period [n = 11 (S) or 5 (R)]. Left ventricular tissue beta-AR protein and mRNA were quantified by Western blot analysis and RT-PCR, respectively. Because beta(2)-ARs are located in caveolae, caveolin-3 was also quantified. beta(1)-AR gene expression decreased ( approximately 5-fold), beta(2)-AR gene expression was not changed, and the ratio of beta(2)-AR to beta(1)-AR gene expression was significantly increased in susceptible compared with resistant dogs. beta(1)-AR protein decreased ( approximately 50%) and beta(2)-AR protein increased (400%) in noncaveolar fractions of the cell membrane in susceptible dogs. Exercise training returned beta(1)-AR gene expression to levels seen in resistant animals but did not alter beta(2)-AR protein levels in susceptible dogs. These data suggest that beta(1)-AR gene expression was decreased in susceptible dogs compared with resistant dogs and, further, that exercise training improves beta(1)-AR gene expression, thereby restoring a more normal beta-AR balance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Death, Sudden, Cardiac / prevention & control
  • Disease Susceptibility / metabolism
  • Disease Susceptibility / therapy
  • Dogs
  • Exercise Therapy / methods*
  • Myocardial Ischemia / metabolism
  • Myocardial Ischemia / therapy
  • Physical Conditioning, Animal / methods*
  • Receptors, Adrenergic, beta / metabolism*
  • Ventricular Fibrillation / metabolism*
  • Ventricular Fibrillation / therapy*

Substances

  • Receptors, Adrenergic, beta