Open AccessDual Cardiovascular Effects of Endothelin-1 Dissociated by BQ-153, a Novel ETA Receptor Antagonist
Author(s) -
Maria Cirino,
Bruno Battistini,
Mitsuo Yano,
Ian W. Rodger
Publication year - 1994
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-199410000-00009
Subject(s) - endothelin receptor antagonist , antagonist , endothelin receptor , pharmacology , dual (grammatical number) , endothelin 1 , medicine , receptor , philosophy , linguistics
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 circulation effects, ET-1 produced consistent and reproducible reductions in renal blood flow (RBF 105 +/- 16 to 21 +/- 6 mm Hg; p < or = 0.004) that lasted approximately 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)