Ra. Beswick et al., NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat, HYPERTENSIO, 38(5), 2001, pp. 1107-1111
Citations number
25
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
We previously reported increased aortic reactive oxygen species (ROS) produ
ction in mineralocorticoid (deoxycorticosterone acetate [DOCA]-salt) hypert
ensive 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 xanthi
ne oxidase inhibitor allopurinol did not significantly change O-2(-) produc
tion. Furthermore, de-endothelialization of aorta from DOCA-salt rats did n
ot affect O-2(-) production compared with that of sham-operated rats. Thus,
xanthine oxidase and uncoupled endothelial NO synthase were not responsibl
e for increased O-2(-) production in the DOCA-salt rats. In contrast, treat
ment with the NADPH oxidase inhibitor apocynin significantly decreased O-2(
-) production in aortic rings from DOCA-salt rats compared with sham-operat
ed rats. Moreover, long-term administration of apocynin (in drinking water,
1.5 mmol/L, 28 days) to DOCA-salt rats significantly decreased systolic bl
ood pressure compared with that of rats treated with DOCA-salt alone. Furth
ermore, 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 dem
onstrated that DOCA-salt rats have significantly greater mRNA levels of the
NADPH oxidase subunit p22phox than do sham-operated rats. These findings s
uggest 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.