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The roles of nitric oxide synthases (NOS) in kidney function are still controversial, principally due to the lack of isoform-specific inhibitors of NOS.To investigate the relative roles of each isoform of NOS in regulation of sodium and volume homeostasis.We studied the effects of long-term modifications of sodium diet and blood pressure on expression of NOS mRNA in the renal cortex, where the three isoforms of NOS are present.We used quantitative reverse transcription-polymerase chain reaction assays specific to each isoform of NOS to determine amounts of their respective mRNA in control rats, deoxycorticosterone acetate (DOCA)-salt hypertensive rats, rats fed a high salt diet, and furosemide-treated rats fed a low-sodium diet. Nicotinamide adenine nucleotide phosphate H (NADPH) diaphorase staining was performed on DOCA-salt and control rat kidneys.Levels of NOS I mRNA in DOCA-salt rats were decreased by treatment, those in low-salt-diet rats remained unaffected and those in high-salt diet rats tended to be intermediate between those of the other rat groups. Expression of NOS III mRNA was not significantly modified by either treatment. Levels of NOS II mRNA in DOCA-salt rats were increased, those in high-salt-diet rats remained unaffected, and those in low-salt-diet were decreased by treatment, but these levels are more than 100-fold lower than those observed for the other isoforms of NOS. NADPH diaphorase staining in macula densa of DOCA-salt rats was markedly decreased compared with that in macula densa of control rats but staining in renal inflammatory and fibrous lesions became detectable, and staining in the vessels did not differ from that for control rats.Our results show that intake of sodium and extracellular fluid volume regulate levels of mRNA of the three NOS isoforms in the renal cortex differently, suggesting that each of them plays a specific role.