In vitro effects of organophosphorus pesticide malathion on the reactivity of rat aorta

Abstract

In vitro studies have demonstrated organophosphate‐mediated vasodilator effects, suggesting that organophosphates may have peripheral activity independent of acetylcholinesterase inhibition. To evaluate the effect of the organophosphate malathion, on the reactivity of isolated rat aorta as well as to explore the mechanisms involved in this response, including the role of nitric oxide (NO) and prostacyclin (PGI2). The study protocol included two methods: in vitro vascular reactivity and flow cytometry (using DAF‐FM DA dye). In rat thoracic aorta segments pre‐constricted with phenylephrine (Phe), malathion induced vasodilation in arteries with endothelium. Acetylcholine‐mediated vasodilatation was not affected when incubate with malathion. Malathion‐mediated vasodilation was blocked by L‐NAME a non‐specific nitric oxide synthase inhibitor and/or indomethacin, an unspecific cyclooxygenase inhibitor. In thoracic aortas rings, with endothelium, Phe promoted dose‐dependent contraction, which was reduced by malathion. In rings with endothelium incubated with malathion and the two blockers, the Phe contraction, was 100% restored. The role of NO was confirmed using flow cytometry. Malathion causes endothelium‐dependent relaxation mediated synergistically by NO (cGMP pathway) and PGI2 (cAMP pathway) that would be a preventive mechanism against spasm and thrombosis. Research support FAEPA.