ENDOTHELIN CONTRIBUTES TO THE HEMODYNAMIC-EFFECTS OF VASOPRESSIN IN SPONTANEOUS HYPERTENSION

Changes in blood pressure, cardiac output, and total peripheral conduc tance evoked by intravenous infusions of [Arg(8)]-vasopressin (vasopre ssin) were recorded before and after pretreatment with bosentan, a non -selective endothelin antagonist, in conscious unrestrained spontaneou sly hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The presser e ffects of vasopressin were exaggerated in SHR compared to WKY. Pretrea tment with bosentan failed to change hemodynamic responses of WKY to v asopressin, but it blunted the increases in blood pressure and the dec reases in conductance evoked by vasopressin in SHR. In contrast, bosen tan failed to change cardiac output responses of SHR to vasopressin. E xcept at the highest dose of vasopressin, bosentan abolished the exagg erated presser responsiveness of the SHR to vasopressin. The results s uggest that endothelin contributes to the exaggerated presser responsi veness of SHR to vasopressin, and that this effect is exerted at the l evel of the resistance vessels and not on factors that regulate cardia c output. (C) 1997 Elsevier Science B.V.