The role of nitric oxide and the renin-angiotensin system in salt-restricted Dahl rats

To elucidate the role of nitric oxide (NO) and renin angiotensin system (RA S) in the development of salt-sensitive hypertension, we investigated the p resser responses and renal histologic changes after long-term inhibition of endogenous NO synthesis in Dahl-Iwai salt-sensitive (DS) and salt-resistan t (DR) rats under salt-restricted conditions that exaggerate RAS activation . Male DS and DR rats (6 weeks old) were fed with a low-salt (0.3%) diet fo r 5 weeks, N-G-nitro-L-arginine (L-NA: dissolved in 60 mg/L deionized water ), an arginine analogue acting as a NO-inhibitor, was also administered for 5 weeks. L-NA administration induced a gradual increase in systolic blood pressure (SBP) in both strains, and the presser response in DS rats was app arently more enhanced relative to that in DR rats. Urinary nitrate plus nit rite (u-NOx) excretion was decreased by L-NA, with a significant negative c orrelation between SEP and u-NOx excretion in DS rats but not in DR rats. P lasma renin activity and urinary aldosterone level were significantly incre ased in L-NA-treated DS rats on week 5. Marked histologic changes with glom erular sclerosis and increased protein-uria and urinary N-acetyl-beta -gluc osaminidase excretion were found in L-NA-treated DS rats but not DR rats. C ompetitive RT-PCR of mRNA extracted from the glomeruli revealed that angiot ensin II type 1 receptor (AT(1)R) mRNA level was significantly lower in DS rats than in DR rats at week 2, and that L-NA administration significantly reduced glomerular AT(1)R level of DS rats at week 5, possibly because of d ownregulation. Our results showed that, even under sodium restriction, the presser response and renal injury induced by chronic NO inhibition were mar kedly more enhanced in DS rats than in DR rats, which indicates that deplet ion of NO participates in both the development of hypertension and glomerul ar injury in DS rats through a potential activation of RAS irrespective of sodium loading. These data suggest that endogenous NO is an essential deter minant of salt-sensitive hypertension in DS rats. (C) 2001 American Journal of Hypertension, Ltd.