title: Heme oxygenase-1 induction improves ischemic renal failure: role of nitric oxide and peroxynitrite.
abstract: The present study evaluated the effects of heme oxygenase-1 (HO-1) induction on the changes in renal outer medullary nitric oxide (NO) and peroxynitrite levels during 45-min renal ischemia and 30-min reperfusion in anesthetized rats. Glomerular filtration rate (GFR), outer medullary blood flow (OMBF), HO and nitric oxide synthase (NOS) isoform expression, and renal low-molecular-weight thiols (-SH) were also determined. During ischemia significant increases in NO levels and peroxynitrite signal were observed (from 832.1 +/- 129.3 to 2,928.6 +/- 502.0 nM and from 3.8 +/- 0.7 to 9.0 +/- 1.6 nA before and during ischemia, respectively) that dropped to preischemic levels during reperfusion. OMBF and -SH significantly decreased after 30 min of reperfusion. Twenty-four hours later, an acute renal failure was observed (GFR 923.0 +/- 66.0 and 253.6 +/- 55.3 microl.min(-1).g kidney wt(-1) in sham-operated and ischemic kidneys, respectively; P < 0.05). The induction of HO-1 (CoCl(2) 60 mg/kg sc, 24 h before ischemia) decreased basal NO concentration (99.7 +/- 41.0 nM), although endothelial and neuronal NOS expression were slightly increased. CoCl(2) administration also blunted the ischemic increase in NO and peroxynitrite (maximum values of 1,315.6 +/- 445.6 nM and 6.3 +/- 0.5 nA, respectively; P < 0.05), preserving postischemic OMBF and GFR (686.4 +/- 45.2 microl.min(-1).g kidney wt(-1)). These beneficial effects of CoCl(2) on ischemic acute renal failure seem to be due to HO-1 induction, because they were abolished by stannous mesoporphyrin, a HO inhibitor. In conclusion, HO-1 induction has a protective effect on ischemic renal failure that seems to be partially mediated by decreasing the excessive production of NO with the subsequent reduction in peroxynitrite formation observed during ischemia.
authors: Departamento de Fisiología, Facultad de Medicina, Universidad de Murcia, 30100 Murcia, Spain. mgsalom@um.es
authors: Miguel G
authors: MG
authors: Salom
authors: Susana Nieto
authors: SN
authors: Cerón
authors: Francisca
authors: F
authors: Rodriguez
authors: Bernardo
authors: B
authors: Lopez
authors: Isabel
authors: I
authors: Hernández
authors: José Gil
authors: JG
authors: Martínez
authors: Adoración Martínez
authors: AM
authors: Losa
authors: Francisco J
authors: FJ
authors: Fenoy
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D003035:Cobalt / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007511:Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007527:Isoenzymes / Q000378:metabolism; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008665:Metalloporphyrins; D013438:Sulfhydryl Compounds; C518404:stannous mesoporphyrin; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D003035:Cobalt; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C018021:cobaltous chloride