| Abstract: | Cardiovascular and renal responses to a step-up infusion of endothelin-1 (ET-1) (1, 5, and 15 ng kg-1 min-1) were investigated in conscious dogs. In addition, the disappearance of ET-l in arterial and central venous plasma after an infusion of 10 ng kg-1 min-1 was quantified, and the effects of vasopressin (AVP, 10 ng kg-1 min-1) and angiotensin II (AII, 2, 5, and 10 ng kg-1 min-1) on plasma ET-1 were investigated. The step-up infusion of ET-1 increased the plasma level from 3.6 ± 0.3 to 243 ± 23 pg ml-1. Concomitantly, arterial blood pressure increased and heart rate (HR) decreased dose-dependently. Diuresis, sodium, and potassium excretion did not change significantly. However, free water clearance increased during the infusion. Clearance of creatinine and excretion of urea decreased (39 ± 4 to 29 ± 3 ml min-1 and 87 ± 16 to 71 ± 14 μmol min-1, respectively). Decay curves for ET-1 in venous and arterial plasma were identical, and initial t½ was 1.1 ± 0.1 min. Vasopressin increased arterial blood pressure (107 ± 4 to 136 ± 3 mmHg) beyond the infusion period and increased plasma ET-1 (85%). An equipressor dose of AII tended to decrease plasma ET-1. It is concluded that the lung is apparently not important in the removal of ET-1, that the disappearance of ET-1 follows a complex pattern, and vasopressin – in contrast to angiotensin II – is able to increase the plasma concentration of ET-1. The latter may suggest that ET-1 is involved in the prolonged pressor action of AVP observed. |
