Chronic beta-agonist administration affects cardiac function of adult but not old rats, independent of beta-adrenoceptor density

Am J Physiol Heart Circ Physiol. 2005 Jul;289(1):H344-9. doi: 10.1152/ajpheart.01254.2004. Epub 2005 Feb 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / administration & dosage*
  • Adrenergic beta-Agonists / pharmacology
  • Aging*
  • Animals
  • Body Weight / drug effects
  • Cardiac Output / drug effects
  • Cardiomegaly / chemically induced
  • Cardiomegaly / physiopathology
  • Coronary Circulation / drug effects
  • Drug Administration Schedule
  • Fenoterol / administration & dosage*
  • Fenoterol / pharmacology
  • Heart / drug effects
  • Heart / physiopathology*
  • Heart Rate / drug effects
  • Male
  • Myocardial Contraction / drug effects
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Organ Size / drug effects
  • Rats
  • Rats, Inbred F344
  • Receptors, Adrenergic, beta / metabolism*

Substances

  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta
  • Fenoterol