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.
Patnaude
L A
LA
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, USA.
Undem
B J
BJ
O'Rourke
S T
ST
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