2009 Southern Regional Meeting Abstracts

Purpose of Study: A chronic activation of the renin-angiotensin-aldosterone system contributes to a loss of skeletal muscle to eventuate in a wasting syndrome termed cardiac cachexia. In 8-wk-old young adult rats receiving chronic aldosterone/salt treatment (ALDOST), a failure to gain body weight is seen and includes skeletal muscle atrophy and bone resorption. Responsible mechanisms are under investigation. In this context, ALDOST is accompanied by increased urinary and fecal excretory losses of Zn leading to hypozincemia, together with skeletal muscle atrophy and a downregulation of Zn²⁺-dependent insulin growth factor (IGF)-1, which mediates the growth-promoting actions of growth hormone. We hypothesized it possible to reverse muscle wasting seen at wk 4 of ALDOST by cotreating rats with either Zn alone or Zn plus IGF-1.
Methods Used: Eight-week-old male Sprague-Dawley rats received ALDO (0.75 μg/h by implanted minipump) together with 1% NaCl and 0.4% KCl in drinking water for 8 wks. At wk 4 of ALDOST, cotreatment was initiated and continued for 4 wks: a ZnSO₄ supplement (dietary, 40 mg/day), which earlier studies indicated would prevent hypozincemia; or ZnSO₄ plus IGF-1 (1.5 mg/kg/day by implanted minipump). At wk 8 we monitored: body weight and skeletal muscle (gastrocnemius) weight. Age-/gender-matched rats served as controls.
Summary of Results: As compared to controls, body weight at wk 8 ALDOST was reduced (381±5 vs. 240±16 g; p<0.05). This failure to gain weight was not prevented by ZnSO₄ supplement (228±12 g) or ZnSO₄ plus IGF-1 (234±8 g). Skeletal muscle weight was reduced at wk 8 ALDOST compared to controls (0.41±0.05 vs. 0.78±0.02 g; p<0.05) and this atrophy of muscle was not prevented by ZnSO₄ supplement (0.38±0.02 g) or ZnSO₄ plus IGF-1 (0.40±0.02 g).
Conclusions: Chronic aldosteronism in growing rats is accompanied by a failure to gain weight and skeletal muscle atrophy. The established muscle wasting seen at wk 4 ALDOST is not reversed by 4-wk treatment with a ZnSO4 supplement or ZnSO₄ plus IGF-1 which suggests the need to reverse aldosteronism before a recovery in wasting can be expected.