CEREBROVASCULAR AND CORONARY EFFECTS OF ENDOTHELIN-1 IN THE GOAT

In vivo and in vitro effects of endothelin-1 (ET- 1) on cerebral and coronary vasculature of goats were examined and compared. In six anesthetized goats intravenous injections of ET-1 (0.1-0.8 nmol) increased arterial pressure, did not change the middle cerebral (MCA) and left anterior descending or left circumflex coronary (LCC) arterial blood flows (electromagnetically measured), and increased cerebral and coronary vascular resistances. In four other anesthetized goats intra-arterial injections of ET-1 (0.01-0.3 nmol) decreased the MCA flow less than the LCC flow (maximal reduction was 20 and 80%, respectively) and only the highest dose increased arterial pressure. In isolated segments from large arteries ET-1 (10(-11) to 10(-7) M) caused concentration-dependent isometric contractions, the concentration causing 50% of the maximal effect and the maximal contraction being lower in cerebral arteries than in coronary arteries. The in vitro reactivity of both arteries was unaffected by endothelium removal or by indomethacin (10(-5) M). Therefore ET-1 produces cerebral and coronary vasoconstriction in vivo and in vitro, probably by acting directly on vascular musculature. Although the sensitivity is higher in isolated cerebral arteries than in coronary arteries, the reactivity in vivo could be lower in the cerebral circulation than in the coronary circulation to this endothelium-derived peptide.