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.

• Authors: P E Ganey, K H Sprugel, K B Hadley, R A Roth
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 237 Issue 1 Pg. 226-31 (Apr 1986) ISSN: 0022-3565 [Print] United States
• PMID: 2937908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ergolines
• Piperidines
• Pyrrolizidine Alkaloids
• Receptors, Serotonin
• Angiotensin II
• Metergoline
• monocrotaline pyrrole
• Serotonin
• Monocrotaline
• Ketanserin

Topics

• Angiotensin II (pharmacology)
• Animals
• Blood Platelets (drug effects)
• Blood Pressure (drug effects)
• Cardiomegaly (chemically induced)
• Ergolines (pharmacology)
• Ketanserin
• Lung (anatomy & histology, drug effects)
• Male
• Metergoline (pharmacology)
• Monocrotaline (analogs & derivatives)
• Organ Size (drug effects)
• Piperidines (pharmacology)
• Pyrrolizidine Alkaloids (pharmacology, toxicity)
• Rats
• Receptors, Serotonin (drug effects)
• Serotonin (physiology)