Role of NAD(P)H oxidase on vascular alterations in angiotensin II-infused mice.

OBJECTIVES: Angiotensin (Ang) II stimulates vascular reactive oxygen species generation via NAD(P)H oxidase activation. We investigated whether vascular NAD(P)H oxidase influences structure and function of resistance arteries from Ang II-infused mice.

METHODS: Mice received Ang II alone (400 ng/kg per min, subcutaneously), Ang II + apocynin (NAD(P)H oxidase inhibitor, 2.5 mg/day, in the food), apocynin alone or Ang II + hydralazine (50 mg/kg per day) for 14 days. Systolic blood pressure (SBP) was measured by tail-cuff methodology and function and structure of small mesenteric arteries were studied in pressurized vessels. Vascular collagen type I/III content was evaluated by confocal immunofluorescence microscopy and by immunoblotting.

RESULTS: The rise in SBP induced by Ang II (P < 0.001) was prevented by apocynin and hydralazine. Media/lumen ratio increase in Ang II-infused mice (P < 0.01) was prevented by apocynin. Acetylcholine-mediated relaxation, which was impaired in Ang II-infused mice (P < 0.001), was improved by apocynin. Confocal microscopy and immunoblotting demonstrated increased collagen type I/III content in mesenteric arteries from Ang II-infused mice. Apocynin, but not hydralazine, prevented the increase in collagen abundance in Ang II-infused mice. The increase in vascular NAD(P)H oxidase activity by Ang II (P < 0.001) was prevented by apocynin.

CONCLUSIONS: The NAD(P)H oxidase inhibitor apocynin reduced blood pressure elevation and prevented structural alterations, endothelial dysfunction, and collagen deposition in the media of small arteries in Ang II-infused mice. Although hydralazine also decreased blood pressure, it had no effects on vascular collagen content. Our findings suggest that NAD(P)H oxidase activity plays an important role in vascular functional and structural changes and in the composition of the vascular wall in Ang II-dependent hypertension.