Hyperfiltration, nitric oxide, and diabetic nephropathy.
Early diabetes is often accompanied by an increased glomerular filtration rate (GFR). This hyperfiltration, which is significantly dependent upon increased nitric oxide activity, is believed to contribute to progression of diabetic nephropathy. In this article, a technique for the measurement of tubular fluid nitric oxide in vivo, in real time, is reviewed, and findings in three commonly used rodent models of diabetes are described. The mechanisms of altered tubuloglomerular feedback (TGF) in diabetes are also reviewed, with emphasis on hyperfiltration and the role of nitric oxide. New findings on the modulation of hyperfiltration in the classic type 2 diabetes db/db mouse are presented, showing suppression of the TGF mechanism and modulation of single-nephron GFR by a specific nitric oxide synthase inhibitor.
Levine
David Z
DZ
The Kidney Research Centre, Ottawa Health Research Institute and University of Ottawa, 451 Smyth Road, Room 1333, Ottawa, Ontario, K1H 8M5 Canada. dzlevine@uottawa.ca