title: NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat.
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 (O(2-)), 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 O(2-) production. Furthermore, de-endothelialization of aorta from DOCA-salt rats did not affect O(2-) production compared with that of sham-operated rats. Thus, xanthine oxidase and uncoupled endothelial NO synthase were not responsible for increased O(2-) production in the DOCA-salt rats. In contrast, treatment with the NADPH oxidase inhibitor apocynin significantly decreased O(2-) 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, O(2-) 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 O(2-) production and possibly contributes to increased blood pressure in the DOCA-salt hypertensive rat.
authors.affiliation: Department of Physiology, Medical College of Georgia, Augusta, USA. rbeswick@umich.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Beswick
authors.forename: A M
authors.initials: AM
authors.lastname: Dorrance
authors.forename: R
authors.initials: R
authors.lastname: Leite
authors.forename: R C
authors.initials: RC
authors.lastname: Webb
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D046508:Culture Techniques; D003900:Desoxycorticosterone; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins; D009252:NADPH Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D013481:Superoxides; D003900:Desoxycorticosterone; C056165:acetovanillone; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase