Endothelin antagonist reduces hemodynamic responses to vasopressin in DOCA-salt hypertension

Yu, Ming, Venkat Gopalakrishnan, Thomas W. Wilson, and J. Robert McNeill. Endothelin antagonist reduces hemodynamic responses to vasopressin in DOCA-salt hypertension. Am J Physiol Heart Circ Physiol 281:H2511-H2517, 2001.--The contribution ofendothelin to the changes in blood pressure, cardiac output, and total peripheral resistance evoked by arginine vasopressin and angiotensin II was investigated in deoxycorticosterone acetate (DOCA)-salt hypertensive rats by infusing the peptides intravenously before and after pretreatment with the endothelin receptor antagonist bosentan. Blood pressure was recorded with radiotelemetry devices and cardiac output was recorded with ultrasonic transit time flow probes in conscious unrestrained animals. The dose-related decreases in cardiac output induced by vasopressin and angiotensin II were unaffected by bosentan. In contrast, the dose-related increases in total peripheral resistance evoked by vasopressin were blunted in both DOCA-salt hypertensive and sham normotensive rats, but this effect of bosentan was greater in the DOCA-salt hypertensive group. In contrast with vasopressin, bosentan failed to change hemodynamic responses to angiotensin II. The exaggerated vascular responsiveness (total peripheral resistance) of the DOCA-salt hypertensive group to vasopressin was largely abolished by bosentan. These results suggest that endothelin contributes to the hemodynamic effects of vasopressin but not angiotensin II in the DOCA-salt model of hypertension. angiotensin II; bosentan; blood pressure; cardiac output; total peripheral resistance; deoxycorticosterone acetate Received 25 April 2001; accepted in final form 17 August 2001