ENDOTHELIN-1 DOES NOT CONTRIBUTE TO ISCHEMIA REPERFUSION-INDUCED VASOCONSTRICTION IN SKELETAL-MUSCLE/

The experiment reported was designed to investigate whether endothelin -1 (ET-1) contributes to vasospasm and poor perfusion during the reper fusion after prolonged ischemia in skeletal muscle. Male Sprague-Dawle y rats weighting 100 to 120 g were anesthetized with Nembutal. The vas cular isolated rat cremaster muscle, coupled with local interarterial infusion, was the model used in this study. The diameters of feeding a rterioles and terminal arterioles were measured utilizing intravital m icroscopy. The number of terminal arterioles with temporary cessation of flow were counted in each cremaster. Group 1: ET-dose response (8 r ats)-various concentrations of ET-1 (from 10(-8) M to 10(-5) M) were i nfused into the cremaster to test whether this muscle was responsive t o the agent in a dose-dependent manner. Group 2: ET-antagonist respons e (12 rats)-PD-142893, 10(-4) M (ETab receptor antagonist) plus ET-1 1 0(-7) M were infused into the cremaster to test whether vasospasm caus ed by exogenous ET-1 could be prevented by pretreatment with this spec ific ETab receptor antagonist. Group 3: ischemia/reperfusion response (12 rats)-PD-142893, 10(-4) M was infused into the cremaster before is chemia (4 hr warm ischemia) and during reperfusion to test whether ETa b receptor antagonism was effective in preventing the vasospasm associ ated with ischemia/reperfusion injury. The results from this study sho w that a mixed ETab endothelin antagonist, PD-142893, infused before i schemia and during reperfusion at a dose which virtually abolished the vasoconstriction produced by a high concentration of exogenous endoth elin-1, had no effect on ischemia/reperfusion-induced vasoconstriction in this model. These results suggest that ET-1 probably does not cont ribute to the ischemia/reperfusion-induced vasoconstriction and poor r eflow in rat skeletal muscle.