Renal ischemia in the rat stimulates glomerular nitric oxide synthesis

Am J Physiol Regul Integr Comp Physiol. 2001 Mar;280(3):R771-9. doi: 10.1152/ajpregu.2001.280.3.R771.

Abstract

Renal ischemia in humans and in experimental animals is associated with a complex and possibly interrelated series of events. In this study, we have investigated the glomerular nitric oxide (NO) production after renal ischemia. Unilateral or bilateral renal ischemia was induced in Wistar rats by clamping one or both renal arteries. NO production was assessed by measuring glomerular production of nitrite, a stable end product of NO catabolism, and NO-dependent glomerular cGMP production and by assessing the glomerular NADPH diaphorase (ND) activity, an enzymatic activity that colocalizes with NO-synthesis activity. Furthermore, we determined the isoform of NO synthase (NOS) implicated in NO synthesis by Western blot and immunohistochemistry. Glomeruli from rats with bilateral ischemia showed elevated glomerular nitrite and cGMP production. Besides, glomeruli from this group of rats showed an increased ND activity, whereas glomeruli from the ischemic and nonischemic rats with unilateral ischemia did not show this increase in nitrite, cGMP, and ND activity. In addition, glomeruli from ischemic kidneys showed an increased expression of endothelial NOS without changes in the inducible isoform. Addition of L-NAME in the drinking water induced a higher increase in the severity of the functional and structural damage in rats with bilateral ischemia than in rats with unilateral ischemia and in sham-operated animals. We can conclude that after renal ischemia, there is an increased glomerular NO synthesis subsequent to an activation of endothelial NOS that plays a protective role in the renal damage induced by ischemia and reperfusion.

MeSH terms

  • Animals
  • Blotting, Western
  • Constriction
  • Creatinine / blood
  • Cyclic GMP / biosynthesis
  • Enzyme Inhibitors / pharmacology
  • Female
  • Immunohistochemistry
  • Ischemia / etiology
  • Ischemia / metabolism*
  • Ischemia / pathology
  • Isoenzymes / metabolism
  • Kidney / blood supply*
  • Kidney / pathology
  • Kidney Glomerulus / metabolism*
  • Kidney Tubules / pathology
  • Microscopy, Electron
  • NADPH Dehydrogenase / metabolism
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type III
  • Nitrites / metabolism
  • Rats
  • Rats, Wistar
  • Renal Artery

Substances

  • Enzyme Inhibitors
  • Isoenzymes
  • Nitrites
  • Nitric Oxide
  • Creatinine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • NADPH Dehydrogenase
  • Cyclic GMP
  • NG-Nitroarginine Methyl Ester