Nitric oxide in the kidney: synthesis, localization, and function.

The characterization and cloning of constitutive and inducible nitric oxide (NO)-synthesizing enzymes and the development of specific inhibitors of the L-arginine NO pathway have provided powerful tools to define the role of NO in renal physiology and pathophysiology. There is increasing evidence that endothelium-derived NO is tonically synthesized within the kidney and that NO plays a crucial role in the regulation of renal hemodynamics and excretory function. Bradykinin and acetylcholine induce renal vasodilation by increasing NO synthesis, which in turn leads to enhancement of diuresis and natriuresis. The blockade of basal NO synthesis has been shown to result in decreases of renal blood flow and sodium excretion. These effects are partly mediated by an interaction between NO and the renin angiotensin system. Intrarenal inhibition of NO synthesis leads to reduction of sodium excretory responses to changes in renal arterial pressure without an effect on renal autoregulation, suggesting that NO exerts a permissive or a mediatory role in pressure natriuresis. Nitric oxide released from the macula densa may modulate tubuloglomerular feedback response by affecting afferent arteriolar constriction. Nitric oxide produced in the proximal tubule possibly mediates the effects of angiotensin on tubular reabsorption. In the collecting duct, an NO-dependent inhibition of solute transport is suggested. The L-arginine NO pathway is also active in the glomerulus. Under pathologic conditions such as glomerulonephritis, NO generation is markedly enhanced due to the induction of NO synthase, which is mainly derived from infiltrating macrophages. An implication of NO in the mechanism of proteinuria, thrombosis mesangial proliferation, and leukocyte infiltration is considered. In summary, the data presented on NO and renal function have an obvious clinical implication. A role for NO in glomerular pathology has been established. Nitric oxide is the only vasodilator that closely corresponds to the characteristics of essential hypertension. Using chronic NO blockade, models of systemic hypertension will provide new insights into mechanisms of the development of high blood pressure.