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.