Effects of beta 1- and beta 1 + beta 2-antagonists on training-induced myocardial hypertrophy and enzyme adaptation.
The effects of beta 1- and beta 1 + beta 2-antagonists on the myocardial adaptation to exercise training were investigated in male Sprague-Dawley rats randomly divided into trained (treadmill, 1 hr/day, 5 days/week for 10 weeks at 27 m/min, 15% grade) without drug (TC), sedentary without drug (SC), trained treated with atenolol (TA) (10 mg/kg body wt, i.p.), trained treated with propranolol (TP, 30 mg/kg body wt, i.p.), and sedentary propranolol. Doses of both beta-antagonists were titrated to decrease the exercise heart rate by 25% compared to the controls. The heart weight and heart/body weight ratio were significantly greater in TC (1.28 +/- 0.07 g (P less than 0.01); 296 +/- 12 mg/100 g body wt (P less than 0.05) respectively) than in SC (1.09 +/- 0.04 g and 268 +/- 11 mg/100 g body wt), or in TP and TA. Myocardial mitochondrial protein was unchanged by training or beta-blockade. Citrate synthase and beta-hydroxyacyl CoA dehydrogenase activities were not altered. Carnitine palmitoyltransferase activity was increased in SP compared to SC. Training increased hexokinase activity only in TC (5.22 +/- 0.12 vs 4.26 +/- 0.23 mumol/min/g wet wt, P less than 0.01). Lactate dehydrogenase activity increased significantly (P less than 0.01) in both TC (383 +/- 14 mumol/min/g wet wt) and TA (372 +/- 14 mumol/min/g wet wt) compared to SC (276 +/- 14 mumol/min/g wet wt), but not in TP versus SP. These data indicate that (1) beta-adrenergic blockade prevents training-induced cardiac hypertrophy; (2) beta-antagonists have little effect on the myocardial oxidative capacity; and (3) while the training induction of myocardial hexokinase is inhibited by both beta 1- and beta 1 + beta 2-antagonists, myocardium may increase its ability to utilize lactate during exercise with training despite beta 1-blockade.
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000032:analysis; D000222:Adaptation, Physiological / Q000187:drug effects*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control*; D002334:Carnitine O-Palmitoyltransferase / Q000032:analysis; D002950:Citrate (si)-Synthase / Q000032:analysis; D006339:Heart Rate / Q000187:drug effects; D006593:Hexokinase / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010084:Oxidation-Reduction; D010806:Physical Education and Training; D011506:Proteins / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D000319:Adrenergic beta-Antagonists; D007773:Lactates; D011506:Proteins; D019344:Lactic Acid; D015094:3-Hydroxyacyl CoA Dehydrogenases; D007770:L-Lactate Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase; D006593:Hexokinase