Background and Purpose: There is a remarkable paucity of studies analyzing the role of the endothelium-derived relaxing factors on the vascular effects of organophosphates. This study was carried out to evaluate the vascular effects of malathion and the role of nitric oxide (NO) and prostacyclin (PGI2). Methods: Vascular reactivity measuring isometric forces in vitro (‘organ chambers') and flow cytometry (cells loaded with DAF-FM DA) were used. Results: In rat thoracic aorta segments contracted with phenylephrine (Phe) (10-7 mol/l), malathion (10-10 to 10-5 mol/l) induced concentration-dependent relaxation in arteries with intact endothelium (n = 7; p < 0.05). Malathion-mediated relaxation was blocked by N-nitro-L-arginine methyl ester (L-NAME; 10-4 mol/l), a nonspecific NO synthase inhibitor, and/or indomethacin (10-5 mol/l), a nonspecific cyclooxygenase inhibitor (n = 10, p < 0.05). In thoracic aorta rings, with and without endothelium, Phe (10-10 to 10-5 mol/l) evoked concentration-dependent contraction, which was reduced in the presence of malathion. In rings with or without endothelium, incubated with malathion, L-NAME and indomethacin, the Phe-induced contraction was restored. The role of NO was confirmed using flow cytometry. Malathion evokes endothelium-dependent relaxation through the M1 muscarinic receptor, since this relaxation was clearly blocked by atropine (M1 and M2 blocker) and pirenzepine (M1 blocker), but was less blocked by gallamine (M2 blocker) or 4-DAMP (M3 blocker). Conclusions: These findings suggest that the organophosphate compound effects on vascular reactivity depend of NO and PGI2.

Worek F, Koller M, Thiermann H, Szinicz L: Diagnostic aspects of organophosphate poisoning. Toxicology 2005,214:182-189.
Kurek A: Effect of cholinesterase (ChE) reactivators on hemodynamics in animals. 2. Reactions of the circulatory and respiratory systems of dogs after administration of ChE reactivators. Pol Arch Weter 1987;24:485-499.
Lim SL, Sim MK, Loke WK: Acetylcholinesterase-independent action of diisopropyl-flurophosphate in the rat aorta. Eur J Pharmacol 2000;404:353-359.
Preston E, Heath C: Atropine-insensitive relaxation and hypotension in the organophosphate-poisoned rabbit. Arch Int Pharmacodyn Ther 1972;200:231-244.
Preston E, Heath C: Depression of the vasomotor system in rabbits poisoned with an organophosphate anticholinesterase. Arch Int Pharmacodyn Ther 1972;200:245-254.
Takahashi H, Kojima T, Ikeda T, Tsuda S, Shirasu Y: Differences in the mode of lethality produced through intravenous and oral administration of organophosphorus insecticides in rats. Fundam Appl Toxicol 1991;16:459-468.
Barr DB, Angerer J: Potential uses of biomonitoring data: a case study using the organophosphorus pesticides chlorpyrifos and malathion. Environ Health Perspect 2006;114:1763-1769.
Osanai T, Fujita N, Fujiwara N, Nakano T, Takahashi K, Guan W, Okumura K: Cross talk of shear-induced production of prostacyclin. Am J Physiol Heart Circ Physiol 2000;278:H233-H238.
Osanai T, Akutsu N, Fujita N, Nakano T, Takahashi K, Guan W, Okumura K: Cross talk between prostacyclin and nitric oxide under shear in smooth muscle cell: role in monocyte adhesion. Am J Physiol Heart Circ Physiol 2001;281:H177-H182.
Radomski MW, Palmer RM, Moncada S: The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol 1987;92:639-646.
Hyslop S, de Nucci G: The mechanisms and significance of the coupled release of endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2) from endothelial cells. Wien Klin Wochenschr 1991;103:422-434.
Vanhoutte PM: Endothelial adrenoceptors. J Cardiovasc Pharmacol 2001,38:796-808.
Celotto AC, Capellini VK, Restini CB, Baldo CF, Bendhack LM, Evora PR: Extracellular alkalinization induces endothelium-derived nitric oxide dependent relaxation in rat thoracic aorta. Nitric Oxide 2010;23:269-274.
Celotto AC, Restini CB, Capellini VK, Bendhack LM, Evora PR: Acidosis induces relaxation mediated by nitric oxide and potassium channels in rat thoracic aorta. Eur J Pharmacol 2011;656:88-93.
Schini VB, Vanhoutte PM: L-Arginine evokes both endothelium-dependent and -independent relaxations in L-arginine-depleted aortas of the rat. Circ Res 1991;68:209-216.
Ryberg AT, Selberg H, Soukup O, Gradin K, Tobin G: Cholinergic submandibular effects and muscarinic receptor expression in blood vessels of the rat. Arch Oral Biol 2008;53:605-616.
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