High pressure induces superoxide production in isolated arteries viaprotein kinase C-dependent activation of NAD(P)H oxidase

Ungvári, Zoltán and Csiszár, Anna and Huang, An and Kaminski, Pawel M. and Wolin, Michael S. and Koller, Ákos (2003) High pressure induces superoxide production in isolated arteries viaprotein kinase C-dependent activation of NAD(P)H oxidase. CIRCULATION, 108 (10). pp. 1253-1258. ISSN 0009-7322


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Background - Oxidative stress seems to be present in all forms of hypertension. Thus, we tested the hypothesis that high intraluminal pressure (P-i) itself, by activating vascular oxidases, elicits increased superoxide (O-2(.-)) production interfering with flow-induced dilation. Methods and Results - Isolated, cannulated rat femoral arterial branches were exposed in vitro ( for 30 minutes) to normal P-i (80 mm Hg) or high P-i (160 mm Hg). High P-i significantly increased vascular O-2(.-) production ( as measured by lucigenin chemiluminescence and ethidium bromide fluorescence) and impaired endothelium-dependent dilations to flow; these effects could be reversed by superoxide dismutase. Administration of the NAD(P)H oxidase inhibitor diphenyleneiodonium, apocynin, the protein kinase C (PKC) inhibitor chelerythrine or staurosporin or the removal of extracellular Ca2+ during high P-i treatment prevented the increases in O-2(.-) production, whereas administration of losartan or captopril had no effect. High P-i resulted in significant increases in intracellular Ca2+ ([Ca2+](i)) in the vascular wall ( fura 2 fluorescence) and phosphorylation of PKCalpha ( Western blotting). The PKC activator phorbol myristate acetate significantly increased vascular O-2(.-) production, which was inhibited by superoxide dismutase, diphenyleneiodonium, chelerythrine, or removal of extracellular Ca2+. Both high P-i and phorbol myristate acetate increased the phosphorylation of the NAD( P) H oxidase subunit p47(phox). Conclusion - High P-i itself elicits arterial O-2(.-) production, most likely by PKC-dependent activation of NAD( P) H oxidase, thus providing a potential explanation for the presence of oxidative stress and endothelial dysfunction in various forms of hypertension and the vasculoprotective effect of antihypertensive agents of different mechanisms of action.

Item Type: Article
Subjects: R Medicine / orvostudomány > RZ Other systems of medicine / orvostudomány egyéb területei
Depositing User: MTMT SWORD
Date Deposited: 28 Jan 2014 12:47
Last Modified: 28 Jan 2014 12:47

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