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-agonist administration affects cardiac function of adult but not old rats, independent of -adrenoceptor density
1 Physiology, The University of Melbourne, Melbourne, Victoria, Australia
2 Agriculture, Charles Sturt University, Wagga Wagga, New South Wales, Australia
* To whom correspondence should be addressed. E-mail: gsl{at}unimelb.edu.au.
Although 
-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 aims of this study were to determine whether chronic -agonist administration impairs cardiac function in adult or aged rats. Adult (16 mo) and aged (28 mo) Fischer 344 rats were treated with either fenoterol (1.4 mg/kg/day, i.p. injection), or vehicle for 4 weeks. Heart function was assessed in vitro prior to analyses of cardiac structure and -adrenoceptor density. Heart mass was 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 increased left ventricular developed pressure, marked reduction in cardiac output, and reduced 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 -adrenoceptor density, but rather an age-related increase in downregulation following treatment. Our results show that chronic -agonist treatment impairs cardiac function to a greater extent in adult than aged rats. These results provide important information regarding the potential effects of chronic -agonist usage on cardiac function and for the future development of safe and effective treatments for sarcopenia.
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