COORDINATE REGULATION OF RENAL EXPRESSION OF NITRIC-OXIDE SYNTHASE, RENIN, AND ANGIOTENSINOGEN MESSENGER-RNA BY DIETARY SALT

Experiments were performed to examine the effect of changes in dietary salt intake on the neuronal form of the constitutive nitric oxide syn thase (ncNOS, type I NOS), renin, and angiotensinogen mRNA expression in the kidney Three groups of Sprague-Dawley rats were studied as foll ows: rats maintained on a 3% Na diet plus 0.45% NaCl in the drinking f luid for 7 days (high salt), rats given a single injection of furosemi de (2 mg/kg ip) and a 0.03% Na diet for 7 days (low salt), and rats on a diet containing 0.2% Na (control). mRNA expression was assessed wit h reverse transcription-polymerase chain reaction (RT-PCR) methods usi ng cDNA prepared from samples of renal cortex and microdissected tubul ar segments. ncNOS PCR products were quantified by comparison with a d ilution series of a mutant deletion template. Compared with their resp ective control, ncNOS mRNA levels in renal cortical tissue were elevat ed in rats on a low-salt diet and reduced in rats on a high-salt diet. Similar changes were seen in the expression of renin and angiotensino gen mRNA. Dietary salt intake did not alter the mRNA levels for ncNOS from the inner medulla or for endothelial constitutive NOS (ecNOS, typ e III NOS) and inducible NOS (iNOS, type II NOS) in the renal cortex. ncNOS mRNA was found in glomeruli dissected with the macula densa-cont aining segment (MDCS), but only at marginal levels in glomeruli withou t MDCS. Furthermore, a low-salt diet stimulated ncNOS mRNA in glomerul i with MDCS by 6.2-fold compared with a high-salt diet. There was no e ffect of salt diet on ncNOS mRNA in glomeruli without MDCS or in inner medullary collecting ducts. These results suggest that ncNOS expressi on in macula densa cells is inversely regulated by salt intake, thus f ollowing the known response of the renin-angiotensin system to changes in salt balance.