Chronic beta-agonist administration affects cardiac function of adult but not old rats, independent of beta-adrenoceptor density.
Although beta-adrenoceptor agonists have clinical merit for attenuating the age-related loss of skeletal muscle mass and strength (sarcopenia), potential cardiac-related side effects may limit their clinical application. The aim of this study was to determine whether chronic beta-agonist administration impairs cardiac function in adult or aged rats. Adult (16 mo) and aged (28 mo) Fischer 344 rats were treated with fenoterol (1.4 mg.kg(-1).day(-1) ip) or vehicle for 4 wk. Heart function was assessed in vitro before analyses of cardiac structure and beta-adrenoceptor density. Heart mass increased 17% and 25% in fenoterol-treated adult and aged rats, respectively. The increased heart mass in aged, but not adult, rats was associated with a relative increase in collagen content. Cardiac hypertrophy in adult rats was associated with an increase in left ventricular developed pressure, a marked reduction in cardiac output, and a reduction in coronary flow per unit heart mass. In contrast, negligible differences in ventricular function were observed in fenoterol-treated aged rats. The differential effect on contractile function was not associated with age-related differences in beta-adrenoceptor density but, rather, an age-related increase in downregulation after treatment. Our results show that chronic beta-agonist treatment impairs cardiac function to a greater extent in adult than in aged rats. These results provide important information regarding the potential effects of chronic beta-agonist use on cardiac function and the future development of safe and effective treatments for sarcopenia.
Gregorevic
Paul
P
Dept. of Physiology, The Univ. of Melbourne, Victoria 3010, Australia.
Ryall
James G
JG
Plant
David R
DR
Sillence
Martin N
MN
Lynch
Gordon S
GS
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D000375:Aging; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects; D004334:Drug Administration Schedule; D005280:Fenoterol / Q000008:administration & dosage* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D005280:Fenoterol