Aerobic muscle contraction impaired by serotonin-mediated vasoconstriction

Vasoconstriction mediated by serotonin (5-HT) inhibits muscle metabolism in resting constant-flow-perfused rat hindlimb and may do so by vascular shunting. In the present study, the effects of 5-HT on tension development and contraction-induced oxygen uptake by the sciatic nerve-stimulated gastrocnemius-plantaris-soleus muscle group of the perfused rat hindlimb and tension development by electrically stimulated isolated incubated soleus and extensor digitorum longus muscles were examined. In both erythrocyte and erythrocyte-free perfusions, 0.25 microM 5-HT increased perfusion pressure and markedly decreased contraction-induced tension, oxygen uptake, and lactate release. The release of metabolic vasodilators from exercising skeletal muscle did not appear to affect 5-HT-mediated vasoconstriction; rather, vascular resistance increased during the period of muscle contraction. In contrast, vasoconstriction during muscle contraction mediated by alpha-adrenoceptor stimulation did not impair tension and was partially overcome by metabolic vasodilators. In addition, contraction of isolated incubated soleus and extensor digitorum longus muscles was not affected by 5-HT addition to the incubation medium. We conclude that 5-HT impairs contractility of working muscle during the aerobic phase by limiting oxygen delivery through redistributing perfusate flow. The results are consistent with a vasoconstrictor action of 5-HT on larger vessels, perhaps at feed arteries external to the working muscle. When constricted by 5-HT, these vessels are apparently insensitive to metabolic vasodilatation.