title: Exercise training normalizes beta-adrenoceptor expression in dogs susceptible to ventricular fibrillation.
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.
authors.affiliation: Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210-1218, USA.
authors.forename: Bethany J
authors.initials: BJ
authors.lastname: Holycross
authors.forename: Monica
authors.initials: M
authors.lastname: Kukielka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nishijima
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Altschuld
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Carnes
authors.forename: George E
authors.initials: GE
authors.lastname: Billman
mesh_terms: D000818:Animals; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D004198:Disease Susceptibility / Q000378:metabolism / Q000628:therapy; D004285:Dogs; D005081:Exercise Therapy / Q000379:methods*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000628:therapy; D010805:Physical Conditioning, Animal / Q000379:methods*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014693:Ventricular Fibrillation / Q000378:metabolism* / Q000628:therapy*
chemical_list: D011943:Receptors, Adrenergic, beta