Gregorevic Paul, Ryall James G, Plant David R, Sillence Martin N, Lynch Gordon S
Dept. of Physiology, The Univ. of Melbourne, Victoria 3010, Australia.
Am J Physiol Heart Circ Physiol. 2005 Jul;289(1):H344-9. doi: 10.1152/ajpheart.01254.2004. Epub 2005 Feb 25.
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.
尽管β-肾上腺素能受体激动剂在减轻与年龄相关的骨骼肌质量和力量损失（肌肉减少症）方面具有临床价值，但潜在的心脏相关副作用可能会限制其临床应用。本研究的目的是确定长期给予β-激动剂是否会损害成年或老年大鼠的心脏功能。成年（16个月）和老年（28个月）的Fischer 344大鼠接受非诺特罗（1.4毫克·千克⁻¹·天⁻¹，腹腔注射）或赋形剂治疗4周。在分析心脏结构和β-肾上腺素能受体密度之前，对心脏功能进行体外评估。非诺特罗治疗的成年和老年大鼠心脏质量分别增加了17%和25%。老年大鼠心脏质量增加，但成年大鼠未增加，这与胶原蛋白含量的相对增加有关。成年大鼠的心脏肥大与左心室舒张末压升高、心输出量显著降低以及单位心脏质量的冠状动脉血流量减少有关。相比之下，在非诺特罗治疗的老年大鼠中，心室功能的差异可忽略不计。对收缩功能的不同影响与β-肾上腺素能受体密度的年龄相关差异无关，而是与治疗后下调的年龄相关增加有关。我们的结果表明，长期β-激动剂治疗对成年大鼠心脏功能的损害程度大于老年大鼠。这些结果为长期使用β-激动剂对心脏功能的潜在影响以及肌肉减少症安全有效治疗方法的未来发展提供了重要信息。
