Increased expression of endothelial iNOS accounts for hyporesponsiveness of pulmonary artery to vasoconstrictors after paraquat poisoning.

Abstract

Paraquat is a toxic herbicide that induces severe acute lung injury (ALI) and pulmonary hypertension in humans. Although vascular disorders are present and contribute to increased mortality in ALI patients, there is little data available on vascular responsiveness after toxic exposure to paraquat. We aimed to evaluate the vascular response of isolated pulmonary arteries from rats treated with a dose of paraquat that induces ALI. Paraquat treatment did not modify the relaxant response of pulmonary artery to acetylcholine, but greatly reduced phenylephrine-induced contraction. Removal of the endothelium, inhibition of nitric oxide synthase (NOS) with L-NAME or selective inhibition of inducible NOS (iNOS) with L-NIL, restored contraction of vessels from paraquat poisoned rats to the same level as those not exposed to paraquat. The basal production of NO and expression of iNOS were increased in endothelium-intact but not in endothelium-denuded vessels from paraquat-poisoned rats. Expression of endothelial NOS was not modified. Our findings suggest that paraquat poisoning increases endothelial iNOS expression and basal NO production decreasing responsiveness of pulmonary artery to vasoconstrictors. Thus, our results do not support the hypothesis that pulmonary hypertension in paraquat-induced ALI is mediated by a reduction in endothelial NO production or increased contractility of pulmonary artery.

• Authors: Leticia B R Zocrato, Luciano S A Capettini, Bruno A Rezende, Josiane F Silva, Maria da Glória Rodrigues-Machado, Steyner F Cortes, Virginia S Lemos
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 24 Issue 3 Pg. 1019-25 (Apr 2010) ISSN: 1879-3177 [Electronic] England
• PMID: 20004239 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Herbicides
• Nitrites
• Vasoconstrictor Agents
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Paraquat
• NG-Nitroarginine Methyl Ester

Topics

• Acute Lung Injury (pathology)
• Animals
• Blotting, Western
• Dose-Response Relationship, Drug
• Endothelium, Vascular (drug effects, metabolism)
• Enzyme Inhibitors (pharmacology)
• Herbicides (poisoning)
• In Vitro Techniques
• Male
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (biosynthesis)
• Nitric Oxide Synthase Type III (biosynthesis)
• Nitrites (metabolism)
• Paraquat (poisoning)
• Pulmonary Artery (drug effects, enzymology)
• Rats
• Rats, Wistar
• Vasoconstrictor Agents (pharmacology)