DIETARY SALT LOADING DECREASES THE EXPRESSIONS OF NEURONAL-TYPE NITRIC-OXIDE SYNTHASE AND RENIN IN THE JUXTAGLOMERULAR APPARATUS OF ANGIOTENSINOGEN GENE-KNOCKOUT MICE

The present study investigates whether neuronal type nitric oxide synt hase (N-NOS) in the macula densa participates in the regulation of ren al renin expression during altered dietary salt intake in angiotensino gen gene-knockout (Atg(-/-)) mice. Wild-type (Atg(+/+)) and Atg(-/-) m ice were fed a low-salt (0.04% NaCl), normal-salt (0.3% NaCl), or high -salt (4% NaCl) diet for 2 wk. Histochemical staining for NADPH diapho rase (NADPHd) and renin were analyzed morphometrically. Levels of N-NO S and renin mRNA in renal cortical tissues were determined by reverse transcription-PCR and Northern blot analysis, respectively. In animals fed a normal-salt diet, the renal expressions of N-NOS and renin were markedly increased in Atg(-/-) mice compared with Atg(+/+) mice. When mutant mice were fed a high-salt diet, the signal intensity of the NA DPHd reaction and the number of positively stained macula densa cells were significantly decreased. The levels of renal cortical N-NOS mRNA were also suppressed by the treatment. These changes were paralleled b y decreases in renal renin-immunoreactive areas and the levels of reni n mRNA. On the other hand, salt restriction did not produce further si gnificant increases in the renal N-NOS and renin expressions in mutant mice, whereas a parallel inverse relationship was observed between th ese enzyme expressions and the levels of salt intake in wild-type mice . These results aug gest that the N-NOS expression in the macula densa is inversely regulated by salt intake and that the enzyme activity is functionally linked to renal renin production. Salt-modulated renal N -NOS and renin expressions are independent on angiotensin formation in Atg(-/-) mice.