2009 Southern Regional Meeting Abstracts

Purpose of Study: Chronic activation of the renin-angiotensin-aldosterone system (RAAS) is accompanied by a progressive loss of soft tissue. To examine pathophysiologic responses involved in muscle wasting, we employ a model of aldosteronism in rats, where a failure to gain weight is seen, together with skeletal muscle atrophy. In this context, aldosterone/salt treatment (ALDOST) is associated with increased excretory losses of Zn and a consequent hypozincemia, together with a downregulation of Zn-dependent insulin growth factor (IGF)-1, a mediator of the growth promoting properties of growth hormone. We hypothesized a Zn supplement or IGF-1 given alone or in combination would prevent the failure to gain weight and skeletal muscle atrophy.
Methods Used: Uninephrectomized 8-week-old male Sprague-Dawley rats received ALDO by implanted minipump (0.75 μg/h) for 4 wks, together with 1% NaCl/0.4% KCl in drinking water. A subgroup of these rats were given a ZnSO₄ supplement (dietary, 40 mg/day) or IGF-1 (1.5 mg/kg/day by minipump) alone or in combination. Age-/gender-matched rats served as controls. Four wks later, we monitored body weight and skeletal muscle (gastrocnemius) weight.
Summary of Results: Body weight at 12 wks of age in control rats (290±4 g) was not attained in rats receiving 4 wks ALDOST (234±10 g; p<0.05) and this failure to gain weight was not prevented by cotreatment with either ZnSO₄ supplement (247±6 g) or IGF-1 (256±8g) alone or ZnSO₄ plus IGF-1 (208±8 g). A wasting of skeletal muscle was seen with 4 wks ALDOST compared to controls (0.50±0.02 vs. 0.60±0.02 g; p<0.05). Cotreatment with ZnSO₄ (0.51±0.02 g) or IGF-1 (0.44±0.02 g) alone or ZnSO₄ plus IGF 1 (0.44±0.02 g) did not prevent muscle wasting.
Conclusions: In growing rats receiving 4 wks ALDOST, a failure to gain weight and skeletal muscle wasting is found and is not prevented by cotreatment with ZnSO₄ supplement or IGF-1 given alone or in combination. These findings suggest that unless aldosteronism is corrected, other strategies will not prevent muscle wasting.