NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat

Richard A. Beswick, Anne M. Dorrance, Romulo Leite, R. Clinton Webb

Research output: Contribution to journalArticle

273 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1107-1111
Number of pages5
JournalHypertension
Volume38
Issue number5
DOIs
StatePublished - 2001

Keywords

  • Deoxycorticosterone acetate
  • Hypertension, mineralocorticoid
  • Mineralocorticoids
  • NADH/NADPH

ASJC Scopus subject areas

  • Internal Medicine

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