Dual cardiovascular effects of endothelin-1 dissociated by BQ-153, a novel ETA receptor antagonist

Journal of Cardiovascular Pharmacology
M CirinoI W Rodger

Abstract

Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide that elicited both vasodilator and vasoconstrictor responses in anesthetized pigs. Within 1.0 min after the first injection of ET-1 (0.4 nmol/kg, intravenously, i.v.) there was a transient decrease in mean arterial pressure (MAP 82 +/- 4 to 64 +/- 5 mm Hg; p < or = 0.01). The vasodepressor response was accompanied by reductions in left ventricular (LV) + dp/dtmax (1,834 +/- 104 to 1,493 +/- 87 mm Hg/s, p < or = 0.001), LV - dp/dt (2,600 +/- 149 to 1,865 +/- 136 mm Hg/s; p < or = 0.001) and cardiac output (CO 2.6 +/- 0.1 to 2.0 +/- 0.1 L/min, p < or = 0.001). The short (< 3.0 min) vasodilatory phase was followed by a prolonged (> 15 min) vasopressor response in which MAP (82 +/- 4 to 103 +/- 5 mm Hg; p < or = 0.001) and pulmonary arterial pressure (PAP 11 +/- 1 to 15 +/- 1 mm Hg; p < or = 0.01) increased. With each subsequent dose (0.4 nmol/kg i.v.) of ET-1, the initial vasodilatory component diminished progressively, only a monophasic vasoconstrictor response was observed after the fourth dose. The reductions in CO progressively decreased from 2.6 to 0.1 to 1.7 +/- 0.1 L/min (p < or = 0.001) by the end of the experiment. In contrast to the systemic circ...Continue Reading

Citations

Jan 1, 1996·Pharmacology & Therapeutics·G A Gray, D J Webb
May 2, 2002·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Alexei V Agapitov, William G Haynes
Jun 1, 1997·Journal of Cardiovascular Pharmacology·M CirinoI W Rodger
Oct 30, 1998·Journal of Hypertension·W G Haynes, D J Webb

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