Histological evidences of reparative and regenerative effects of beta-adrenoceptor agonists, clenbuterol and isoproterenol, in denervated rat skeletal muscle.

The aim of this study was to determine the contribution of beta-adrenoceptor activation in the reconstruction of the structural and functional organization of denervated skeletal muscle. beta-agonists, clenbuterol (1.2 mg/kg body weight) and isoproterenol (2 mg/kg body weight), administration (daily oral administration; maximum 7 days) to normal innervated rats as well as denervated animals caused muscle hypertrophy. An increase in mean fiber diameter confirmed this stimulated growth both in normal innervated and denervated rat gastrocnemius muscle. Examination of muscle nuclei from treated but normal innervated rat gastrocnemius exhibited features like large size, active nucleoplasm and an increase in their number per fiber cross section and per mm mean fiber length indicating towards an elevated biosynthetic activity in tissue in the presence of beta adrenoceptor agonists. Administration of drugs to normal innervated animals resulted in an emergence of central muscle nuclei. The hyperactive and enlarged muscle nuclei ultimately organized themselves into unusually elongated nuclear streaks. beta agonist treatment to denervated rats resulted in amelioration of atrophic state of tissue characterized by hypertrophy of muscle fibers thus lending to a restoration of structural organization of tissue. Bizarre shapes of nuclei in denervated muscle tend to recover to that characteristic to normal innervated muscle in presence of clenbuterol and isoproterenol hydrochloride. All observations were confirmed by administering butoxamine, a beta-adrenoceptor antagonist along with beta-agonists. The results suggests that both clenbuterol and isoproterenol hydrochloride are capable of mimicking normal innervation functions in skeletal muscle and thus play important role in the structural and functional reorganization of tissue. Amelioration of denervation atrophy in rat gastrocnemius in the presence of beta-agonists supports this.

Isoproterenol ameliorates workstress-induced rat skeletal muscle degeneration.

Beta-Agonists though have been widely studied for their protein anabolic effects in skeletal muscles, but the lipid status under work stress and agonist treatment have not been understood well in the skeletal muscles and heart of rat. In the present study, adult male Wistar rats were subjected to work overload stress and beta agonist isoproterenol treatment (2 mg kg(-1) day(-1) intraperitoneally) to examine, whether it attenuates work stress-induced changes or not. Simultaneously, beta2 antagonist butoxamine (2 mg kg(-1) day(-1) intraperitoneally) was administered to another isoproterenol-treated group. Work stress led to myofibrillar degeneration as well as rapid utilization of lipid to meet increased energy demands and for muscle repair, which was reflected through histochemical localization of lipids and biochemical estimation of cholesterol and triglycerides. Significantly decreased cholesterol levels in skeletal muscles and heart muscles were noticed. As expected, isoproterenol reversed the conditions by raising cholesterol and triglyceride levels significantly in the skeletal muscles and also by ameliorating the degenerative changes in muscle fibres as induced by work overload. However, severe accumulation of lipids in heart infers towards deleterious effects of isoproterenol on heart and thus remains a limiting factor for its immediate clinical application. Further research is needed to separate desirable effects of beta agonists on skeletal muscles from any undesirable effects on the heart, so as to optimize their therapeutic potential.

Clenbuterol induced changes in cholesterol and triglyceride levels of gastrocnemius, pectoralis and heart of rat under work induced stress.

Work induced stress led to decreased cholesterol and fluctuating triglyceride levels in gastrocnemius and pectoralis muscles in rats. But the drug (clenbuterol, 2 mg kg(-1) day(-1)) treatment increased cholesterol and triglyceride levels in both the muscles. However, heart showed decreased cholesterol and increased triglyceride level in the animals under work stress, but at the same time drug treatment led to a significant increase in levels of the two lipid fractions, inferring towards deleterious effect of the drug on heart.