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REGIONAL AND MUSCLE SPECIFIC EFFECTS OF A Я-ADRENERGIC AGONIST IN HINDLIMB SUSPENDED RATS.     D.A. von Deutsch^1,2,3, I. K. Abukhalaf^1,2,4, L.E. Wineski^1,3, S.A. Pitts^1,3, R. Roper^1,2, L.D. Kataria^1,2, D.C. Jackson^1,2, D.E. Potter^1,2 and D.F. Paulsen^1,3.  ¹NASA Space Medicine and Life Science Research Center, ²Department of Pharmacology and Toxicology, ³Department of Anatomy, ⁴Clinical Research Center, Morehouse School of Medicine, Atlanta GA.

Exposure to microgravity and prolonged bed-rest results in head-ward fluid shifts. The impact of these changes on skeletal muscle are of particular interest. Clenbuterol (Cb) was used because it is the most potent anabolic agent amongst the Я2-adrenergic family of drugs. The regional, dose-dependent, and muscle specific effect(s) of clenbuterol in hindlimb-suspended and non-suspended mature male rats were investigated. In non-suspended rats, 0.4 mg/kg clenbuterol has been observed to have a greater anabolic effect on muscle mass in the leg [(EDL), plantaris, soleus, and gastrocnemius] as opposed to the thigh [(ADL) and pectineus]. This regional effect was not apparent with the 1.0 mg/kg treatment in non-suspended rats.  Specifically, the thigh muscle (ADL) was the least responsive to clenbuterol's (1.0 mg/kg) anabolic effect and showed the greatest reduction in mass to unloading.  The leg muscles (plantaris and EDL) were the most responsive to clenbuterol (1.0 mg/kg) in suspended rats. Unloading and clenbuterol treatment resulted in distinctly different responses by the soleus, EDL, and plantaris muscles. Soleus showed a moderate anabolic effect of slower onset in response to clenbuterol in loaded muscle. Plantaris showed modest anabolic effect in loaded muscle, but the onset of clenbuterol’s action was more immediate.  Significant changes in polyamine levels were observed in loaded and unloaded muscles as well as between clenbuterol treated and untreated muscles.  Clenbuterol (1.0 mg/kg) reduced the loss of body weight in both suspended and non-suspended rats and resulted in a significant reduction in the amount of mesenteric fat (more than 50% reduction). 

(Supported by NASA GRANTS: NAG9-971, NCC-9-53, NIH GRANT P20RR11104-05.)