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

• Published in: American journal of physiology. Renal physiology Vol. 296; no. 1; pp. F25 - F33
• Main Authors: Kwon, Osun, Hong, Seok-Min, Ramesh, Ganesan
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.01.2009
• Subjects: Acute Kidney Injury - metabolism; Acute Kidney Injury - pathology; Adolescent; Adult; Aged; Case-Control Studies; Child; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Female; Humans; Hypothesis testing; Injuries; Kidney Transplantation - pathology; Kidney Tubules, Distal - blood supply; Kidney Tubules, Distal - metabolism; Kidney Tubules, Distal - pathology; Kidneys; Male; Middle Aged; Neurons; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type I - metabolism; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type III - metabolism; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Transplantation, Homologous; Young Adult
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.90531.2008

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.