Objective: NAD(P)H oxidase is thought to be a main source of vascular free radicals production in most forms of hypertension. In this study, we hypothesized that p47phox, a NAD(P)H oxidase subunit, contributes blood pressure(BP) elevation and cardio-renal hypertrophy and vascular alterations. Methods: Male p47phox-/- mice and Wild type (WT; C57BL/6) mice aged at 7 week, 3, 6, and 12 month were studied (n=8 each group). SBP measurements were monitored by tail-cuff method. Wet heart and kidney were measured to evaluate hypertrophy. Structural(media to lumen ratio) and functional alterations were evaluated in mesenteric arteries using a pressurized myograph. Endothelium-dependent or -independent relaxation was assessed by measuring the dilatory responses to acetylcholine or sodium nitropusside(SNP). The NAD(P)H oxidase activity was measured using lucigenin chemiluminescence. The mRNA expression of NAD(P)H oxidase subunits were quantified by real-time PCR. Results: Systolic BP elevation shown in WT(p for trend, 0<0.05) was slightly blunted in p47phox-/- mice, and they showed a significant difference, particularly at 12 month in p47phox-/- mice(109±4.2 mmHg vs. 118±6.5 mmHg of WT, P<0.05). Cardiac and renal weights were similar between 2 groups during the study period. Media to lumen ratio in mesenteric artery were lower significantly at 12 months in p47phox-/- mice(6.0±0.2% vs. 6.5±0.3 % of WT, P<0.01). However, its ratio was not different at 7 weeks, 3, and 6 months in 2 groups. Vasodilatory responses to a maximal dose of acetylcholine were well preserved until 6 months in both groups, however, WT mice at 12 months showed a decreased vasorelaxation to 81±10.3%, in contrast to 97±1.2% of vasorelaxation in p47phox-/- mice. SNP response was similarly well preserved in both groups. gp91phox subunit increased progressively in p47phox-/- mice(P for trend<0.05), in contrast to no further increase in WT. p67phox expression showed a trend of decrease in WT without changes in p47phox-/- mice. Conclusions: p47phox, NAD(P)H oxidase subunit, contributed BP elevation and arterial remodeling, suggesting that p47phox blockade may prevent hypertension development and its organ damage developed by ageing.
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