Diminished NO generation by injured endothelium and loss of macula densa nNOS may contribute to sustained acute kidney injury after ischemia-reperfusion

Osun Kwon, Seok Min Hong, Ganesan Ramesh

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

In postischemic acute kidney injury (AKI) or acute renal failure, a dissipation of glomerular filtration pressure is associated with an altered renal vascular tone and reactivity, as well as a loss of vascular autoregulation. To test the hypothesis that renal nitric oxide (NO) generation reflects endothelial damage in the kidney after ischemia-reperfusion, we quantified the urinary NO levels and identified the site of its generation in postischemic AKI. Subjects were 50 recipients of cadaveric renal allografts: 15 with sustained AKI and 35 with recovering renal function. Urine and blood samples were obtained after transplant, and intraoperative allograft biopsies were performed to examine NO synthases (NOSs) in the kidney. In the sustained AKI group, urinary nitrite and nitrate excretion (in μmol/g urine creatinine) was lower (12.3 ± 1.8 and 10.0 ± 1.4 on postoperative days 0 and 3) than in the recovery group [20.0 ± 3.6 and 35.1 ± 5.3 (P < 0.005 vs. sustained AKI on days 0 and 3) on postoperative days 0 and 3]. Endothelial NOS expression diminished from the peritubular capillaries of 6 of 7 subjects in the sustained AKI group but from only 6 of 16 subjects in the recovery group. No differences were observed in the inducible NOS staining pattern between the two groups. Neuronal NOS staining was rarely observed in the macula densae of subjects but was prominent in control tissues. These findings suggest that a diminished NO generation by injured endothelium and loss of macula densa neuronal NOS could impair the vasodilatory ability of the renal vasculature and contribute to the reduction in the glomerular filtration rate in postischemic AKI.

Original languageEnglish (US)
Pages (from-to)F25-F33
JournalAmerican Journal of Physiology - Renal Physiology
Volume296
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • Acute renal failure
  • Confocal microscopy
  • Nitric oxide synthase
  • Vasculature

ASJC Scopus subject areas

  • Physiology
  • Urology

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