title: A protective role for endothelial nitric oxide synthase in glomerulonephritis.
abstract: In acute glomerulonephritis (GN), increased nitric oxide (NO) production occurs, suggesting a pathophysiological role for NO in the disease process. Although NO potentially could have both toxic as well as protective effects, its exact role in the pathophysiology of GN is unclear and may depend on the NOS isoform generating NO. The protective effects of NO such as prevention of leukocyte and platelet activation and adhesion have been attributed to NO generated by endothelial nitric oxide synthase (eNOS). Evidence for a beneficial role for eNOS includes the demonstration of reduced eNOS expression in experimental models of GN as well as human biopsy specimens that is mostly likely due to endothelial cell necrosis. Reduced NO production in GN also may occur through reaction of NO with superoxide anions or the myeloperoxidase (MPO)/hypochlorous acid (HOCL) system. Further evidence has been provided by the observation that in several experimental models of GN, glomerular injury is exacerbated following treatment with non-selective NO inhibitors. Finally, the development of GN is severely aggravated in mice lacking a functional gene for eNOS as compared to wild-type mice, providing direct support for a protective role of eNOS-derived NO in acute GN.
authors.affiliation: Department of Clinical and Experimental Immunology, Cardiovascular Research Institute, University Maastricht, Universiteitssingel 50 6221 ER Maastricht, The Netherlands. p.heeringa@immuno.unimaas.nl
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
authors.forename: Eric
authors.initials: E
authors.lastname: Steenbergen
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
mesh_terms: D000818:Animals; D019610:Cytoprotection / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005921:Glomerulonephritis / Q000503:physiopathology*; D006801:Humans; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III
chemical_list: D004791:Enzyme Inhibitors; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III