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(Hypertension. 2005;45:1062.)
© 2005 American Heart Association, Inc.

Hypertension Highlights

Recent Advances in the Regulation of Nitric Oxide in the Kidney

From the Division of Hypertension and Vascular Research (M.H., J.L.G.), Henry Ford Hospital and Department of Physiology (J.L.G.), Wayne State University, Detroit, Mich.

Correspondence to Jeffrey L. Garvin, Division of Hypertension and Vascular Research, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202. E-mail jgarvin1{at}hfhs.org

Nitric oxide (NO) plays important roles in the regulation of renal function and the long-term control of blood pressure. New roles of NO have been proposed recently in diabetes, nephrotoxicity, and pregnancy. NO derived from all 3 NOS isoforms contributes to the overall regulation of kidney function, and recent advances in our understanding of their regulation have been made lately. In this regard, substrate and cofactor availability play important roles in regulating nitric oxide synthase (NOS) activity not only by limiting enzyme activity but also by influencing the coupling of NOS with its cofactors, tetrahydrobiopterin and NADPH. Protein–protein interactions are now recognized to be important negative and positive regulators of NOS. Phosphorylation is another component of the mechanism whereby NOS is activated or deactivated. Increased NOS expression can also influence enzyme activity; however, the degree of expression does not always correlate with enzyme activity because increased NO levels can result in inhibition of NOS. Finally, other potential regulators of NOS such as endogenous L-arginine analogs may also be important. In this article, we summarize recent advances in the regulation of activity and expression of the NOS isoforms within the kidney.

Key Words: hemodynamics • nitric oxide • nitric oxide synthase • sodium

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