The biochemical actions of phentolamine and papaverine on rat perfused skeletal muscle.

The direct actions of the vasodilators, papaverine and phentolamine, on skeletal muscle metabolism were investigated in an isolated perfusion system. Eviscerated male rats were hemisected above the diaphragm and perfused, via the aorta, with a physiological perfusion medium containing erythrocytes. Papaverine, but not phentolamine, reduced vascular resistance throughout the 80 min study. Papaverine caused marked reductions in muscle concentrations of ATP and phosphocreatine, when compared with muscle from preparations without added vasodilators. This was accompanied by elevations in lactate concentrations. Water content of papaverine-treated muscle was also higher than values in unperfused muscle taken in-vivo. Phentolamine, in contrast, had no effect on muscle ATP, phosphocreatine, lactate or water content. The metabolism of the entire preparation was also investigated. Papaverine induced increases in lactate output while phentolamine treatment caused an initial uptake, followed by an increased output of lactate. There was no significant effect of either papaverine or phentolamine on the metabolism of K+ and glucose. Arteriovenous differences in oxygen-saturation of haemoglobin and pH were also unaltered. Investigations on aspects of protein metabolism demonstrated that papaverine and phentolamine caused significant reductions in muscle protein synthesis when compared with control perfusions or in-vivo values. The reductions in synthesis were not due to reductions in cAMP or limitations in branched-chain amino acid supply. However, there was the suggestion that phentolamine caused a decrease in protein breakdown. The overall data indicated that papaverine and phentolamine may cause impairment of skeletal muscle metabolism. This has important implications for their therapeutic or experimental use.