Hypertension. 2001;38:1107-1111
doi: 10.1161/hy1101.093423
doi: 10.1161/hy1101.093423
(Hypertension. 2001;38:1107.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
NADH/NADPH Oxidase and Enhanced Superoxide Production in the Mineralocorticoid Hypertensive Rat
From the Department of Physiology, Medical College of Georgia (A.M.D., R.C.W.), Augusta; Department of Physiology, University of Michigan (R.A.B.), Ann Arbor; and Department of Pharmacology, Federal University of Minas Gerais (R.L.), Belo Horizonte, Brazil.
Correspondence to Dr Richard A. Beswick, Department of Physiology, Medical College of Georgia, Augusta, GA 30912-3000. E-mail rbeswick{at}umich.edu
Abstract—— We previously reported increased aortic reactive oxygen species (ROS) production in mineralocorticoid (deoxycorticosterone acetate [DOCA]-salt) hypertensive rats. In the present study, we tested the hypothesis that NADH/NADPH oxidase is responsible for increased ROS production, namely superoxide (O2-), in aorta from the DOCA-salt rat. Treatment of aortic rings from DOCA-salt rats with the NO synthase inhibitor N-nitro-L-arginine and the xanthine oxidase inhibitor allopurinol did not significantly change O2- production. Furthermore, de-endothelialization of aorta from DOCA-salt rats did not affect O2- production compared with that of sham-operated rats. Thus, xanthine oxidase and uncoupled endothelial NO synthase were not responsible for increased O2- production in the DOCA-salt rats. In contrast, treatment with the NADPH oxidase inhibitor apocynin significantly decreased O2- production in aortic rings from DOCA-salt rats compared with sham-operated rats. Moreover, long-term administration of apocynin (in drinking water, 1.5 mmol/L, 28 days) to DOCA-salt rats significantly decreased systolic blood pressure compared with that of rats treated with DOCA-salt alone. Furthermore, O2- production in aortic rings from DOCA-salt rats treated with apocynin for 28 days was reduced compared with that of untreated DOCA-salt rats. Reverse transcriptase–polymerase chain reaction (RT-PCR) analysis demonstrated that DOCA-salt rats have significantly greater mRNA levels of the NADPH oxidase subunit p22phox than do sham-operated rats. These findings suggest that NADPH oxidase is increased and is responsible for increased O2- production and possibly contributes to increased blood pressure in the DOCA-salt hypertensive rat.
Key Words: deoxycorticosterone acetate • NADH/NADPH • mineralocorticoids • hypertension, mineralocorticoid
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