ACUTE AND CHRONIC EFFECTS OF DEXFENFLURAMINE ON THE PORCINE PULMONARY-ARTERY

1. Studies were designed to investigate the responses of isolated pulm onary arteries from control pigs or pigs chronically treated with dexf enfluramine (7.2 mg/kg per day orally for 4 weeks). 2. Rings with and without endothelium were suspended in organ chambers for recording of isometric tension. 3. Dexfenfluramine (10(-9) to 10(-6) M) did not aff ect vascular tone, but at higher concentrations caused contractions th at were not affected by indomethacin, methiothepin, the presence of en dothelium or by the chronic treatment. 4. Chronic treatment augmented the endothelium-dependent relaxations to serotonin and aggregating pla telets but not those to adenosine diphosphate. It did not affect the c ontraction or rings without endothelium evoked by platelets, nor the r elaxation to SIN-1, a nitric oxide donor. The maximal contraction to e ndothelin-1 (but not that of norepinephrine) was impaired in treated p igs. 5. These results show that dexfenfluramine causes contraction of isolated porcine pulmonary arteries only at concentrations higher than 3 x 10(-6) M, and that chronic treatment with dexfenfluramine potenti ates the endothelium-dependent relaxations to serotonin and aggregatin g platelets in the porcine pulmonary artery without affecting their di rect effect on the smooth muscle. (C) 1998 Elsevier Science Inc.