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Contractile mechanisms of endothelin, a newly isolated vasoactive substance from endothelium, were evaluated in anterior cerebral arteries (ACA). Furthermore, the effects of thiopental, pentobarbital, ketamine, and diltiazem on the endothelin-induced cerebral vasoconstriction were also studied. Endothelin induced cerebral arterial contractions in concentrations above 3 X 10(-10) M. The median effective concentration (ED50: X10(-9) M) of endothelin was 2.1 +/- 0.7 (n = 6). Endothelin did not elicit contractions in preparations soaked in Ca2(+)-free solution, but addition of 2.5 mM Ca2+ to the baths induced marked contractions. Thiopental and pentobarbital attenuated endothelin-induced contractions at concentrations above 3 X 10(4) M, while ketamine was effective above 10(-3) M. In contrast, diltiazem decreased endothelin-induced vasoconstriction at 10(-6) M. The findings suggest that endothelin may cause contractions of porcine cerebral arteries by influx of Ca2+ through Ca2+ channels. The cerebral vasomotion induced by endothelin, however, does not seem to be influenced by clinical doses of barbiturates and ketamine.
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