Tetrahydrobiopterin protects the kidney from ischemia-reperfusion injury

26Citations
Citations of this article
30Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Tetrahydrobiopterin (BH4) is an essential cofactor for the nitric oxide (NO) synthases and represents a critical determinant of NO production. BH4 depletion during ischemia leads to the uncoupling of the synthases, thus contributing to reperfusion injury due to increased superoxide formation. To examine whether BH4 supplementation attenuates ischemia-reperfusion injury, we clamped the left renal arteries of male Lewis rats immediately following right-side nephrectomy. BH4 tissue levels significantly decreased after 45 min of warm ischemia compared with levels in non-ischemic controls. Histopathology demonstrated significant tubular damage and increased peroxynitrite formation. Intravital fluorescent microscopy found perfusion deficits in the microvasculature and leakage of the capillary mesh. Supplemental BH4 treatment before ischemia significantly reduced ischemia-induced renal dysfunction, and decreased tubular histologic injury scores and peroxynitrite generation. BH4 also significantly improved microcirculatory parameters such as functional capillary density and diameter. These protective effects of BH4 on microvasculature were significantly correlated with its ability to abolish peroxynitrite formation. We suggest that BH4 significantly protects against acute renal failure following ischemia reperfusion. Whether BH4 has a therapeutic potential will require more direct testing in humans. © 2010 International Society of Nephrology.

Cite

CITATION STYLE

APA

Sucher, R., Gehwolf, P., Oberhuber, R., Hermann, M., Margreiter, C., Werner, E. R., … Brandacher, G. (2010). Tetrahydrobiopterin protects the kidney from ischemia-reperfusion injury. Kidney International, 77(8), 681–689. https://doi.org/10.1038/ki.2010.7

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free