CHRONIC PATHOPHYSIOLOGIC CIRCULATING ENDOTHELIN LEVELS PRODUCE HYPERTENSION IN CONSCIOUS DOGS

Although recent studies have reported endogenous plasma endothelin (ET ) levels to be elevated two- to fivefold in chronic pathophysiologic s tates, whether such an increase in circulating ET levels alone can lea d to significant long-term alterations in cardiovascular function is n ot known. The purpose of this study was to examine the long-term syste mic hemodynamic effects of a pathophysiologic increase in circulating ET concentration in chronically instrumented, conscious dogs (n = 4). Infusion of endothelin (2.5 mg/kg/min) for 8 days increased plasma con centration of endothelin two- to threefold. ET increased mean arterial pressure from 85 +/- 3 to 103 +/- 3 mm Hg, which was sustained throug hout the period of infusion. Total peripheral resistance was increased by approximately 70%. Cardiac output decreased transiently by 25% and remained below control levels at the termination of ET infusion. Thes e data indicate the importance of pathophysiologic levels of ET in con trolling systemic hemodynamics in chronic conditions. Furthermore, ET may play a role as a mediator of chronic hypertension in pathophysiolo gic states associated with endothelial dysfunction.