Polyamine synthesis blockade in monocrotaline-induced pneumotoxicity

Biochemical Pharmacology
J W OlsonM N Gillespie

Abstract

Based on the documented regulatory role of polyamines in cell growth and differentiation, we have proposed that these organic cations are involved with the development of monocrotaline (MCT)-induced hypertensive pulmonary vascular disease. Two lines of evidence support this hypothesis: (1) MCT causes progressive increases in lung polyamine contents which are temporarily related to the development of cardiopulmonary abnormalities, and (2) blockade of polyamine synthesis with the site-selective enzyme-activated inhibitor, alpha-difluoromethylornithine (DFMO), attenuates development of medial arterial thickening, increased pulmonary arterial pressure, and right ventricular hypertrophy. To evaluate the mechanism of DFMO protection, the present study assessed when, during the course of MCT-induced pneumotoxicity, DFMO exerts its salutary effects, and determined if the protection afforded by DFMO could be reversed through supplementation with exogenous polyamines. To address the first issue, rats were treated with 30 mg/kg MCT and, 10 days after administration when lung polyamine contents were augmented and when pulmonary edema was evident, DFMO treatment was initiated as a 2% solution in the drinking water. In animals receiving MCT ...Continue Reading

References

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Citations

Jan 1, 1990·Pharmacology & Therapeutics·R J Huxtable
Apr 1, 1997·Clinical and Experimental Hypertension : CHE·D W LipkeE E Soltis
Sep 1, 1994·Clinical and Experimental Hypertension : CHE·E E SoltisJ W Olson
Jan 22, 2004·Circulation·Rohit BudhirajaPaul M Hassoun
Oct 22, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mykhaylo RuchkoPavel Babal
Mar 11, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·P H Hoet, B Nemery

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