Nitric oxide synthase isoforms play distinct roles during acute peritonitis

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Abstract

Background. Acute peritonitis is the most frequent complication of peritoneal dialysis (PD). Increased nitric oxide (NO) release by NO synthase (NOS) isoforms has been implicated in acute peritonitis, but the role played by the NOS isoforms expressed in the peritoneum is unknown.Methods. We investigated the structural and functional consequences of acute peritonitis induced by LPS in wild-type (WT) mice versus knockout mice (KO) for the endothelial NOS (eNOS), the inducible NOS (iNOS) or the neuronal NOS (nNOS).Results. The level of NO metabolites (NOx) in the dialysate was maximal 18 h after LPS injection. LPS induced a significant increase in the transport of small solutes and decreased ultrafiltration in WT mice. These changes, which occurred without vascular proliferation, were paralleled by the upregulation of nNOS and eNOS, and the induction of iNOS. The transport modifications induced by LPS were significantly reversed in eNOS KO mice, but not modified in mice lacking iNOS or nNOS. In contrast, the increase of dialysate NOx was abolished in iNOS KO mice and significantly reduced in eNOS KO mice, but left unchanged in mice lacking nNOS. Mice lacking iNOS also showed more severe inflammatory changes, and a trend towards increased mortality following LPS.Conclusion. These data demonstrate specific roles for NOS isoforms in the peritoneal membrane and suggest that selective eNOS inhibition may improve peritoneal transport during acute peritonitis. The Author 2009. Published by Oxford University Press [on behalf of the ERA-EDTA]. All rights reserved.2009Oxford University PressThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses?by-nc/2.0/uk/) which permits unrestricted non-commercial use distribution, and reproduction in any medium, provided the original work is properly cited.

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Ni, J., McLoughlin, R. M., Brodovitch, A., Moulin, P., Brouckaert, P., Casadei, B., … Devuyst, O. (2010). Nitric oxide synthase isoforms play distinct roles during acute peritonitis. Nephrology Dialysis Transplantation, 25(1), 86–96. https://doi.org/10.1093/ndt/gfp415

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