title: Renal carbonic anhydrases are involved in the reabsorption of endogenous nitrite.
abstract: Nitrite (ONO(-)) exerts nitric oxide (NO)-related biological actions and its concentration in the circulation may be of particular importance. Nitrite is excreted in the urine. Hence, the kidney may play an important role in nitrite/NO homeostasis in the vasculature. We investigated a possible involvement of renal carbonic anhydrases (CAs) in endogenous nitrite reabsorption in the proximal tubule. The potent CA inhibitor acetazolamide was administered orally to six healthy volunteers (5 mg/kg) and nitrite was measured in spot urine samples before and after administration. Acetazolamide increased abruptly nitrite excretion in the urine, strongly suggesting that renal CAs are involved in nitrite reabsorption in healthy humans. Additional in vitro experiments support our hypothesis that nitrite reacts with CO(2), analogous to the reaction of peroxynitrite (ONOO(-)) with CO(2), to form acid-labile nitrito carbonate [ONOC(O)O(-)]. We assume that this reaction is catalyzed by CAs and that nitrito carbonate represents the nitrite form that is actively transported into the kidney. The significance of nitrite reabsorption in the kidney and the underlying mechanisms, notably a direct involvement of CAs in the reaction between nitrite and CO(2), remain to be elucidated.
authors.affiliation: Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Kristine
authors.initials: K
authors.lastname: Chobanyan-Jürgens
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schwarz
authors.forename: Anke
authors.initials: A
authors.lastname: Böhmer
authors.forename: Bibiana
authors.initials: B
authors.lastname: Beckmann
authors.forename: Frank-Mathias
authors.initials: FM
authors.lastname: Gutzki
authors.forename: Jan T
authors.initials: JT
authors.lastname: Michaelsen
authors.forename: Dirk O
authors.initials: DO
authors.lastname: Stichtenoth
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsikas
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D000328:Adult; D002245:Carbon Dioxide; D002254:Carbonates; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000378:metabolism*; D003404:Creatinine / Q000652:urine; D005260:Female; D006706:Homeostasis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009566:Nitrates / Q000378:metabolism* / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism* / Q000652:urine; D030421:Peroxynitrous Acid
chemical_list: D002254:Carbonates; D002257:Carbonic Anhydrase Inhibitors; D009566:Nitrates; D009573:Nitrites; D002245:Carbon Dioxide; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D003404:Creatinine; D002256:Carbonic Anhydrases; D000086:Acetazolamide