Control of arterial blood pressure and renal sodium excretion by nitric oxide synthase in the renal medulla

Work in our laboratory has focused on the role of nitric oxide synthase (NO S) in the regulation of renal medullary function. Biochemical studies demon strated that the renal medulla is enriched in immunoreactive NOS protein an d NOS enzymatic activity when compared with the renal cortex. Further exper iments showed large amounts of NOS activity in the inner medullary collecti ng ducts, while moderate NOS activity was found in glomeruli and vasa recta and minimal NOS activity was detected in other nephron segments examined. In subsequent functional studies, selective renal medullary infusion of NOS stimulators (bradykinin or acetylcholine) or inhibitors (L-NAME) preferent ially altered medullary blood flow. The alterations in medullary flow were associated with parallel changes in sodium and water excretion. Similar to the effects observed in anaesthetized rats, chronic infusion of L-NAME dire ctly into the renal medullary interstitial space of conscious, uninephrecto mized SD rats selectively decreased renal medullary blood flow throughout a 5-day L-NAME infusion period. The decrease in medullary blood flow was ass ociated with retention of sodium and the development of hypertension, and t he effects were reversible. In contrast to the effects of chronic NOS inhib ition, renal medullary infusion of NOS substrate L-arginine prevented the d evelopment of sodium-sensitive hypertension in the Dahl salt-sensitive rat placed on a high sodium diet. The data reviewed in this paper indicate that NOS isoforms expressed in the renal medulla have a potent influence on ren al medullary tubular and vascular function with consequential effects on fl uid and electrolyte homeostasis and arterial blood pressure.