Dexfenfluramine-induced contraction of human and rat isolated pulmonary arteries

Mechanisms of dexfenfluramine-induced vasoconstriction were studied in isolated pulmonary arteries suspended in organ baths for isometric tension recording. Dexfenfluramine (10^-7-10^-4 M) caused concentration-dependent contractions in rat and human pulmonary arteries with and without endothelium. In pulmonary arteries of the rat, the response to dexfenfluramine was nearly abolished by treatment with the α-adrenoceptor antagonists, phentolamine (10^-6 M) or prazosin (10^-7 M). In human pulmonary arteries, the concentration-response curve to dexfenfluramine was unaltered by the presence of phentolamine (10^-6 M), prazosin (10^-7 M), ketanserin (10^-6 M), or indomethacin (3x10^-6 M). The results suggest that dexfenfluramine causes contraction of pulmonary vascular smooth muscle by multiple mechanisms, one of which involves activation of α-adrenoceptors within the blood vessel wall. The mechanisms by which dexfenfluramine causes pulmonary vasoconstriction may differ between rat and human pulmonary arteries. Copyright (C) 2000.