This study was performed to examine the hypothesis that increases in endogenous superoxide (O2-) contribute to derangement in renal function leading to salt-sensitive hypertension during chronic nitric oxide synthase (NOS) inhibition. Male Sprague-Dawley rats (230-250 g BW) were fed with diet containing either normal salt (NS, 0.4% NaCl) or high salt (HS, 4% NaCl) and treated with or without NOS inhibitor, nitro-L-arginine methyl ester (L-NAME, 100 mg/L) and O2- scanvenger, tempol (200 mg/L) in drinking water for 4 weeks. Experimental groups were #1, NS only; #2, HS only; #3, NS + L-NAME; #4, HS + L-NAME; #5, NS + L-NAME + tempol; #6, HS + L-NAME + tempol. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography on every 3rd day during the course of 4 weeks. Urine collection was performed in metabolic cages on the day before the start of the treatment and than 7th, 14th, 21st and 28th day to determine water intake and urine output. Sodium and potassium concentration in the urine samples were measured by flame photometer; 8-isoprostane and nitrate/nitrite concentrations were analyzed by enzyme immunoassay. NS and HS diet intake alone for 4 weeks did not alter SBP (groups #1, 127 ± 2 to 133 ± 3; and #2, 129 ± 3 to 136 ± 3 mm Hg). However, L-NAME treatment for 4 weeks resulted in greater increases in SBP in HS rats (group #4, 127 ± 2 to 172 ± 3 mm Hg) than in NS rats (group #2, 128 ± 3 to 156 ± 2 mm Hg). Co-administration of tempol with L-NAME markedly attenuated these hypertensive responses in both NS and HS to a similar level (groups #5, 126 ± 2 to 142 ± 3 and #6, 128 ± 3 to 147 ± 2 mm Hg). Urinary 8-isoprostane excretion (UIsoV) increased in response to L-NAME treatment that was higher in HS rats (group #4, 10.7 ± 0.6 to 21.5 ± 0.8 ng/day) than in NS rats (group #3, 10.6 ± 0.5 to 16.9 ± 0.6 ng/day). Co-treatment with tempol significantly abolished these UIsoV responses to L-NAME treatment in both NS (group #5, 13.8 ± 0.7 ng/day) and HS rats (group #6, 15.8 ± 0.9 ng/day). Urinary nitrate/nitrite excretion (UNoxV) was significantly reduced due to L-NAME treatment in NS rats (group #3, 21.1 ± 1.1 to 14.8 ± 0.9 μmol/day) and in HS rats (group #4, 21.5 ± 2.3 to 11.7 ± 0.7 μmol/day). However, tempol treatment did not alter the L-NAME reduction in UNoxV in both NS (15.6 ± 1.1 μmol/day) and HS rats (13.5 ± 0.9 μmol/day). These data support the hypothesis that O2- contributes to the development of salt sensitivity that involves in the development of NO-deficient form of hypertension.
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