title: Role of nitric oxide in renal medullary oxygenation. Studies in isolated and intact rat kidneys.
abstract: We investigated the role of the endothelial-derived relaxing factor nitric oxide (NO) in the homeostasis of O2 supply to the renal medulla, a region normally operating on the verge of hypoxia. Sensitive Clark-type O2 microelectrodes were inserted into renal cortex and medulla of anesthetized rats. The inhibitor of NO formation, L-NG-monomethylarginine (LNMMA), while increasing blood pressure and reducing renal blood flow, decreased medullary pO2 from 23 +/- 3 mmHg to 12 +/- 3 (P less than 0.001), with no change in the cortex. These responses were promptly reversed by L-arginine, which bypasses the LNMMA blockade. In isolated rat kidneys, LNMMA reduced perfusion flow without altering glomerular filtration rate, and augmented deep medullary hypoxic injury to thick ascending limbs from 68 to 90% of the tubules (P less than 0.02). These changes were prevented by L-arginine. Nitroprusside had a protective effect upon thick limb injury. Finally, in a previously reported model of radiocontrast nephropathy (1988. J. Clin. Invest. 82:401), LNMMA increased the severity of renal failure (final plasma creatinine from 2.3 +/- 2 mg% to 3.4 +/- 3, P less than 0.005) and the proportion of damaged thick limbs (from 24 +/- 6% to 53 +/- 9, P less than 0.01). Nitrovasodilatation may participate in the balance of renal medullary oxygenation and play an important role in the prevention of medullary hypoxic injury.
authors.affiliation: Department of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Brezis
authors.forename: S N
authors.initials: SN
authors.lastname: Heyman
authors.forename: D
authors.initials: D
authors.lastname: Dinour
authors.forename: F H
authors.initials: FH
authors.lastname: Epstein
authors.forename: S
authors.initials: S
authors.lastname: Rosen
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000098:blood supply / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen / Q000032:analysis / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation; D019323:omega-N-Methylarginine
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D010100:Oxygen