High-salt intake enhances superoxide activity in eNOS knockout mice leading to the development of salt sensitivity
Abstract
High-salt intake enhances superoxide activity in eNOS knockout mice leading to the development of salt sensitivity. Am J Physiol Renal Physiol 299: F656-F663, 2010.
First published July 7, 2010; doi:10.1152/ajprenal.00047.2010.-A deficiency in nitric oxide (NO) generation leads to salt-sensitive hypertension, but the role of increased superoxide (O-2(-)) in such salt sensitivity has not been delineated. We examined the hypothesis that an enhancement in O-2(-) activity induced by high-salt (HS) intake under deficient NO production contributes to the development of salt-sensitive hypertension.
Endothelial NO synthase knockout (eNOS KO; total n = 64) and wild-type (WT; total n = 58) mice were given diets containing either normal (NS; 0.4%) or high-salt (HS; 4%) for 2 wk. During this period, mice were chronically treated with a O-2(-) scavenger, tempol (400 mg/l), or an inhibitor of NADPH oxidase, apocynin (1 g/l), in drinking water or left untreated (n = 6-8 per group).
Blood pressure was measured by radiotelemetry and 24-h urine samples were collected in metabolic cages. Basal mean arterial pressure (MAP) in eNOS KO was higher (125 +/- 4 vs. 106 +/- 3 mmHg) compared with WT.
Feeding HS diet did not alter MAP in WT but increased it in eNOS KO to 166 +/- 9 mmHg. Both tempol and apocynin treatment significantly attenuated the MAP response to HS in eNOS KO (134 +/- 3 and 139 +/- 4 mmHg, respectively).
Basal urinary 8-isoprostane excretion rates (UIsoV), a marker for endogenous O-2(-) activity, were similar (2.8 +/- 0.2 and 2.4 +/- 0.3 ng/day) in both eNOS KO and WT mice. However, HS increased UIsoV more in eNOS KO than in WT (4.6 +/- 0.3 vs. 3.8 +/- 0.2 ng/day); these were significantly attenuated by both tempol and apocynin treatment.
These data indicate that an enhancement in O-2(-) activity contributes substantially to the development of salt-sensitive hypertension under NO-deficient conditions.