title: Monocrotaline pyrrole-induced cardiopulmonary toxicity is not altered by metergoline or ketanserin.
abstract: Monocrotaline pyrrole (MCTP) causes endothelial cell damage, pulmonary hypertension and right ventricular hypertrophy in rats by an undetermined mechanism. A role for 5-hydroxytryptamine (5-HT) in the cardiopulmonary response to MCTP has been suggested. To investigate the role of 5-HT, the effects of two 5-HT receptor antagonists were examined in MCTP-treated rats. Cotreatment with metergoline, an antagonist which binds to both 5-HT1 and 5-HT2 receptors, did not alter MCTP-induced elevation of lung weight or right ventricular hypertrophy. 5-HT-induced vascular smooth muscle contractions are mediated by 5-HT2 receptors; therefore, MCTP-treated rats were cotreated with ketanserin (KET), a specific 5-HT2 receptor antagonist. At a dosing regimen of KET that inhibited the 5-HT-induced platelet shape change in platelet-rich plasma and the 5-HT-induced increase in perfusion pressure in isolated lungs, KET did not affect the elevation in lung weight or the increased accumulation of 125I-albumin in the lung tissue of MCTP-treated rats. Moreover, MCTP-induced right ventricular hypertrophy was not attenuated by KET. These results indicate that cotreatment with either of these two 5-HT receptor antagonists does not alter the lung injury or right ventricular hypertrophic response to MCTP and suggest that 5-HT is not necessary for MCTP-induced toxicity.
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced*; D004873:Ergolines / Q000494:pharmacology*; D007650:Ketanserin; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects*; D008297:Male; D008711:Metergoline / Q000494:pharmacology*; D016686:Monocrotaline / Q000031:analogs & derivatives*; D009929:Organ Size / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011763:Pyrrolizidine Alkaloids / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*
chemical_list: D004873:Ergolines; D010880:Piperidines; D011763:Pyrrolizidine Alkaloids; D011985:Receptors, Serotonin; D000804:Angiotensin II; D008711:Metergoline; C014114:monocrotaline pyrrole; D012701:Serotonin; D016686:Monocrotaline; D007650:Ketanserin