EFFECT OF AN ENDOTHELIN ANTAGONIST ON HEMODYNAMIC-RESPONSES TO ANGIOTENSIN-II

We determined changes in blood pressure, cardiac output, and total per ipheral conductance evoked by intravenous infusions of angiotensin II (Ang II) in conscious, unrestrained normotensive Wistar-Kyoto rats (WK Y) and spontaneously hypertensive rats (SHR) before and after pretreat ment with bosentan, a nonselective endothelin antagonist. Blood pressu re was recorded by radiotelemetry and cardiac output by ultrasonic tra nsit-time flow probes. Bosentan per se failed to affect basal blood pr essure and evoked only small changes in cardiac output and total perip heral conductance in both strains. The presser effects of Ang II were exaggerated in SHR compared with WKY. Strikingly, bosentan pretreatmen t blunted the increases in blood pressure, the fall in cardiac output, and the decreases in conductance evoked by lower doses of Ang II but not higher doses of the peptide. This effect was observed in both rat strains but was more pronounced in SHR. These data suggest that endoth elin contributes to the hemodynamic effects of Ang II in both SHR and WKY and that endothelin may contribute to the exaggerated presser resp onsiveness of SHR to Ang II.