LOCALIZATION OF A CONSTITUTIVELY ACTIVE, PHAGOCYTE-LIKE NADPH OXIDASEIN RABBIT AORTIC ADVENTITIA - ENHANCEMENT BY ANGIOTENSIN-II

Superoxide anion (O-2(-)) plays a key role in the endogenous suppressi on of endothelium-derived nitric oxide (NO) bioactivity and has been i mplicated in the development of hypertension, In previous studies, we found that O-2(-) is produced predominantly in the adventitia of isola ted rabbit aorta and acts as a barrier to NO, In the present studies, we characterize the enzyme responsible for O-2(-) production in the ad ventitia and show that this enzyme is a constitutively active NADPH ox idase with similar composition as the phagocyte NADPH oxidase. Constit utive O-2(-)-generating activity was localized to aortic adventitial f ibroblasts and was enhanced by the potent vasoconstrictor angiotensin II, Immunohistochemistry of aortic sections demonstrated the presence of p22(phox), gp91(phox), p47(phox), and p67(phox) localized exclusive ly in rabbit aortic adventitia, coincident with the site of staining f or O-2(-) production, Furthermore, immunodepletion of p67(phox) from a dventitial fibroblast particulates resulted in the loss of NADPH oxida se activity, which could be restored by the addition of recombinant p6 7(phox). Further study into the regulation of this adventitial source of O-2(-) is important in elucidating the mechanisms regulating the bi oactivity of NO and may contribute to our understanding of the pathoge nesis of hypertension.