Nitric oxide synthesis in the kidney: isoforms, biosynthesis, and functions in health

Seminars in Nephrology
Bruce C Kone

Abstract

Nitric oxide (NO) is a gaseous free radical that serves cell signaling, cellular energetics, host defense, and inflammatory functions in virtually all cells. In the kidney and vasculature, NO plays fundamental roles in the control of systemic and intrarenal hemodynamics, the tubuloglomerular feedback response, pressure natriuresis, release of sympathetic neurotransmitters and renin, and tubular solute and water transport. NO is synthesized from L-arginine by NO synthases (NOS). Because of its high chemical reactivity and high diffusibility, NO production by each of the 3 major NOS isoforms is regulated tightly at multiple levels from gene transcription to spatial proximity near intended targets to covalent modification and allosteric regulation of the enzyme itself. Many of these regulatory mechanisms have yet to be tested in renal cells. The NOS isoforms are distributed differentially and regulated in the kidney, and there remains some controversy over the specific expression of functional protein for the NOS isoforms in specific renal cell populations. Mice with targeted deletion of each of the NOS isoforms have been generated, and these each have unique phenotypes. Studies of the renal and vascular phenotypes of these mice h...Continue Reading

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