Endothelin-1 causes a biphasic response in systemic vasculature and increases myocardial contractility in conscious...

We studied the effects of an intravenous (i.v.) bolus of endothelin-1 (ET-1, 0.2 nmol/kg) in conscious rabbits, measuring arterial blood pressure (BP), heart rate (HR), myocardial contractility, and cardiac output and evaluating direct and indirect effects of ET-1 with pacing and pharmacologic antagonists. ET-1 caused a brief initial decrease in BP of 18 +/- 1 mm Hg, followed by a sustained increase of 26 +/- 3 mm Hg (n = 16, p < 0.001). HR increased initially by 60 +/- 11 beats/min and then decreased by 68 +/- 6 beats/min (n = 16, p < 0.001). Left ventricular (LV) dP/dt increased by 2,120 +/- 380 mm Hg/s (n = 5, p < 0.01). LV end-diastolic pressure (LVEDP) increased by 4 +/- 1 mm Hg (n = 5, p < 0.05). Cardiac output (CO) increased initially by 34 +/- 4% and then decreased by 28 +/- 3% (n = 16, p < 0.001). Total peripheral resistance (TPR) decreased initially by 34 +/- 3% and then increased by 72 +/- 13% (n = 16, p < 0.001). Pacing did not alter the effect of ET-1 on arterial BP, LVdP/dt, or LVEDP. The combination of propranolol and scopolamine significantly reduced the increase and decrease in HR and the increase in LVdP/dt. None of the antagonists significantly altered the effect of ET-1 on TPR. ET-1 causes brief initial vasodilation and increased myocardial contractility, followed by sustained vasoconstriction. The vascular effects appear to be of greater significance than the cardiac effects at the dose used.(ABSTRACT TRUNCATED AT 250 WORDS)