ENHANCEMENT OF THE HYPOTENSIVE AND VASODILATOR EFFECTS OF ENDOTOXEMIAIN CONSCIOUS RATS BY THE ENDOTHELIN ANTAGONIST, SB-209670

In conscious, chronically-instrumented rats, the non-selective endothe lin antagonist, SB 209670 (10 mu g kg(-1) min(-1)), caused marked enha ncement of the fall in mean arterial blood pressure during infusion of lipopolysaccharide (LPS) for 24h (LPS alone = -6 +/- 3 mmHg; LPS + SB 209670 = -30 +/- 2 mmHg). This effect was accompanied by a conversion of the mesenteric vasoconstriction to a substantial mesenteric vasodi latation and an augmentation of the hindquarters vasodilatation, seen with LPS alone. Notably, the marked renal hyperaemic vasodilatation du ring LPS infusion was not affected significantly by SB 209670. These r esults indicate that endothelin, directly and/or indirectly, plays a p ivotal role in the cardiovascular sequelae of endotoxaemia in consciou s rats, and prevents marked hypotension, particularly by opposing mese nteric vasodilatation.