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

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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)
JournalAmerican Journal of Physiology - Renal Physiology
Volume296
Issue number1
DOIs
StatePublished - Jan 1 2009

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Acute Kidney Injury
Reperfusion
Endothelium
Nitric Oxide
Ischemia
Nitric Oxide Synthase
Kidney
Allografts
Blood Vessels
Urine
Staining and Labeling
Nitrites
Glomerular Filtration Rate
Nitrates
Creatinine
Homeostasis
Transplants
Biopsy
Pressure

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

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title = "Diminished NO generation by injured endothelium and loss of macula densa nNOS may contribute to sustained acute kidney injury after ischemia-reperfusion",
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.",
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AU - Hong, Seok Min

AU - Ramesh, Ganesan

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N2 - 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.

AB - 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.

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