Published Online
on August 15, 2005

A more recent version of this article appeared on October 1, 2005

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Submitted on April 28, 2005
Revised on May 15, 2005

Superoxide Contributes to Development of Salt Sensitivity and Hypertension Induced by Nitric Oxide Deficiency

Libor Kopkan and Dewan S.A. Majid^*

From Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, La.

^* To whom correspondence should be addressed. E-mail: majid{at}tulane.edu.

Abstract--This study was performed to examine the role of superoxide (O₂^-) in the development of salt sensitivity and hypertension induced by inhibition of nitric oxide (NO) generation. Male Sprague-Dawley rats were fed with diet containing either normal salt (NS) (0.4% NaCl) or high salt (HS) (4% NaCl). These rats were treated with or without an NO synthase inhibitor, nitro-L-arginine methylester (L-NAME) (15 mg/kg/d) and O₂^- scavenger, tempol (30 mg/kg per day) in the drinking water for 4 weeks. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography and urine collection was performed during the course of experimental periods. At the end of 4 weeks, L-NAME treatment resulted in greater increases in SBP in HS rats (127±2 to 172±3 mm Hg; n=8) than in NS rats (130±2 to 156±2 mm Hg; n=9). Co-administration of tempol with L-NAME markedly attenuated these SBP responses to a similar level in both HS (128±3 to 147±2 mm Hg; n=8) and NS rats (126±2 to 142±3 mm Hg; n=8). Urinary 8-isoprostane excretion (U_IsoV) increased in response to L-NAME treatment that was higher in HS (10.6±0.5 to 21.5±0.8 ng/d) than in NS rats (10.8±0.7 to 16.9±0.6 ng/d). Co-treatment with tempol completely abolished these U_IsoV responses to L-NAME in both HS and NS rats but did not alter urinary H₂O₂ excretion rate. The decreases in urinary nitrate/nitrite excretion in response to L-NAME treatment were not altered by co-administration of tempol in both HS and NS rats. These data suggest that enhancement of O₂^- activity during NO inhibition contributes to the development of salt sensitivity that is associated with NO-deficient hypertension.

Key words: hypertension • kidney • nitric oxide

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