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 alpha-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 alpha-adrenoceptors within the blood vessel wall. The mechanisms by which dexfenfluramine causes pulmonary vasoconstriction may differ between rat and human pulmonary arteries.
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, USA.
L A
LA
Patnaude
B J
BJ
Undem
S T
ST
O'Rourke
D000818:Animals; D020372:Dexfenfluramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D017366:Serotonin Receptor Agonists; D020372:Dexfenfluramine