Role of nitric oxide in the control of renal function and salt sensitivity

Abstract

Nitric oxide (NO) plays critical roles in the control of renal and glomerular hemodynamics, tubuloglomerular feedback response, release of renin and sympathetic transmitters, tubular ion transport, and renal water and sodium excretion. This paper explores the importance of NO in the control of renal water and sodium excretion and in the long-term control of arterial blood pressure. Synthesis of NO, characteristics of NO tissue redox forms, NO synthase activity, and NO synthase isoforms in the kidney are reviewed. To define the role of NO as a natriuretic and antihypertensive factor, the most supportive evidence is summarized, and some contradictory results are also noted. Given the evidence that high salt intake results in high NO concentrations and great NO synthase expression and activity selectively in the renal medulla of the kidney, as well as evidence of a deficiency of the NO synthase activity in Dahl salt-sensitive rats confined in the renal medulla, this report emphasizes the mechanisms by which the renal medullary l-arginine/NO system controls sodium excretion and arterial blood pressure. Other mechanisms for the action of NO on sodium homeostasis such as the action on glomerular filtration rate and the direct effect on tubules are also discussed. We conclude that there is strong evidence that under physiologic conditions, NO plays an important role in the regulation of renal blood flow to the renal medulla and in the tubular regulation of sodium excretion. It is thereby involved in the long-term control of arterial blood pressure, and inhibition or deficiency of NO synthase may result in a sustained hypertension.