Skeletal muscle and jejunal protein synthesis in normal and ethanol-treated rats: The effect of the nitric oxide synthase inhibitors, L-ω-nitro-L-arginine methyl ester and N(G)-nitro-L-arginine in vivo

Abstract

The nitric oxide synthase (NOS) inhibitors, L-ω-nitro-L-arginine methyl ester (L-NAME; 25 mg/kg and 100 mg/kg) and N(G)-nitro-L-arginine (L-NNA; 100 mg/kg) were used to investigate the role of NO on in vivo skeletal muscle and jejunal (mucosa and seromuscular layer) protein synthesis rates in normal (ie, untreated) and ethanol-dosed (75 mmol/kg body weight) rats. Fractional rates of protein synthesis, ie, percentage of protein pool renewed each day, ks, %/d) were measured with a flooding dose of L-[3H-4]phenylalanine. In response to both doses of L-NAME and L-NNA, ks in skeletal muscle of normal rats decreased by 9% to 31% (P between <.05 and <.001). In the mucosa, ks was significantly reduced only by the higher dose of L-NAME (−49%, P <.001). In the seromuscular layer, ks was reduced by 15% to 57% (P between <.05 and <.001) in response to both doses of L-NAME and L-NNA. Ethanol dosage reduced ks in skeletal muscle (−35%, P <.001), and small reductions also occurred in the jejunal mucosal and seromuscular layers (−14% P <.05 and −12% P <.05, respectively). However, in the presence of L-NAME, ethanol reduced ks in jejunal mucosal and seromuscular layers by −35% (P <.01) and −30% (P <.01), respectively, compared with controls. This exacerbating effect of L-NAME predosage in ethanol-treated rats was not demonstrable in skeletal muscle. The data thus suggest that (1) endogenous NO facilitates constitutive skeletal muscle and jejunal protein synthesis in control animals in vivo; (2) the sensitivity of jejunal (but not skeletal muscle) protein synthesis to acute ethanol is increased when inhibitors of NOS are used. This tentatively implies that, in response to ethanol, overproduction of NO is not involved in the ethanol-induced reduction of protein synthesis in skeletal muscle or the jejunum. Copyright 2003 Elsevier, Inc. All rights reserved.