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(Hypertension. 2005;46:1026.)
© 2005 American Heart Association, Inc.

Part 2 Original Articles

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

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

Correspondence to Dewan S.A. Majid, MD, PhD, Associate Professor, Department of Physiology, SL 39, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112. E-mail majid{at}tulane.edu

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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