title: Upregulation of cyclooxygenase-2 expression in porcine macula densa with chronic nitric oxide synthase inhibition.
abstract: The objective of this study was to investigate the effects of chronic inhibition of nitric oxide synthase (NOS) on cyclooxygenase-2 (COX-2) expression in the macula densa (MD) of swine, as well as the effects on expression of related proteins. Adult female Yucatan swine were given either tap water (control, n = 6) or water with N (G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/liter, n = 5) for a minimum of 30 days. Duplicate samples of kidney were fixed or snap frozen. There was a significant (P = .0082) upregulation of COX-2 mRNA expression in the MD of L-NAME, as well as an apparent increase in COX-2 protein. Plasma renin activity also increased with L-NAME treatment (control, 0.34 ± 0.08 ng/ml; L-NAME, 1.26 ± 0.03 ng/ml; P = .00000003). There were no differences between groups in expression of either inducible NOS or renin protein or in serum electrolyte concentrations. In conclusion, with chronic inhibition of NOS, COX-2 in MD is upregulated, perhaps to compensate for loss of nitric oxide. Increases in COX-2 products may counteract renal arteriolar constriction and sustain renin release.
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kommareddy
authors.forename: R M
authors.initials: RM
authors.lastname: McAllister
authors.forename: V K
authors.initials: VK
authors.lastname: Ganjam
authors.forename: J R
authors.initials: JR
authors.lastname: Turk
authors.forename: M Harold
authors.initials: MH
authors.lastname: Laughlin
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004573:Electrolytes / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D037901:Euthanasia, Animal; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000201:enzymology; D007668:Kidney / Q000166:cytology / Q000201:enzymology*; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000201:enzymology; D042282:Microdissection / Q000379:methods; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D012083:Renin / Q000378:metabolism; D013552:Swine; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004573:Electrolytes; D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D012333:RNA, Messenger; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester