Plasma levels of nitrites, PGF1 alpha and nitrotyrosine in LPS-treated rats: functional and histochemical implications in aorta

RESUMEN

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ABSTRACT

We investigated the effects of lipopolysaccharide (LPS) administration on plasmanitrite, nitrotyrosine and 6-keto prostaglandin F1 alpha (PGF1 alpha) levels and the relatedresultant changes in function and histochemistry of aorta in rats. Plasma nitrite and PGF1 alpha, nitrotyrosine levels were analysed after 5 mg/kg intravenous LPS was administered to rats compared with those in non-treated rats. The distribution of nitrotyrosinein the aorta was studied immunohistochemically. The contractile responses of aorticrings to phenylephrine (PE) from both the LPS-treated and control rats were studiedin the organ baths. There were increases in plasma nitrite, PGF1á, and nitrotyrosineconcentrations of LPS-treated rats compared to non-treated rats. Immunoreactivityof nitrotyrosine residues were detected in the endothelial and smooth muscle cellsin LPS-treated but not in control rat aorta. The contractile responses to PE of the LPStreatedrat aortic rings were significantly reduced as compared with those of controlrat’s. Incubation of the aortic rings from LPS-treated rats with cyclooxygenaseinhibitor indomethacine or with a combination of indomethacine and nitric oxide synthaseinhibitor Nù-nitro-L-arginine methyl ester (L-NAME) increased the contractileresponses to the levels observed in control rats suggesting that both prostanoids andparticularly nitric oxide (NO) are involved in the reduced contractile responses inLPS-treated rats. These results supported the view that LPS might cause an incrementin both NO and PGI2 levels. This increase in the NO and PGI2 levels may be responsiblefrom the reduction in responses of aorta to contractile agents in LPS-treated rats.Increased peroxynitrite formation in LPS-treated rats may lead to nitration of thetyrosil residues of the proteins in the aorta