Pulmonary vascular responses induced by the pyrrolizidine alkaloid, monocrotaline, in rats

Studies were conducted with isolated segments of pulmonary artery to characterize vessel contractility in monocrotaline-induced pulmonary hypertension. Contractions of pulmonary artery segments from rats given monocrotaline in drinking water (20 mg/l) for up to 20 days were measured in tissue baths. Dose response curves were produced with norepinephrine or serotonin and the response to 120 mM potassium chloride (KCl) was measured. Monocrotaline treatment significantly reduced the KCl-induced maximum contractile responses of pulmonary artery. Norepinephrine-induced maximal contractions (both in terms of mg developed force and as percentage of KCl-induced contractions) decreased with increasing length of monocrotaline treatment. Serotonin-induced maximal contractions were not altered by monocrotaline treatment. A minimum of 4 days treatment with monocrotaline drinking water reduced the contractile responses of pulmonary artery removed 16 days later. In separate experiments using continuous exposure to monocrotaline, a minimum of 15 days treatment was required before contractile activity was significantly altered. Results indicate monocrotaline treatment reduces the contractile activity of muscular pulmonary artery. Alterations in vessel responsiveness were produced after a minimum of 4 days treatment with monocrotaline in drinking water (an estimated exposure of 14-20 mg/kg) but required 15-20 days to develop.