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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Abstract
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 |
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Subjects: | R Medicine / orvostudomány > RZ Other systems of medicine / orvostudomány egyéb területei |
SWORD Depositor: | MTMT SWORD |
Depositing User: | MTMT SWORD |
Date Deposited: | 28 Jan 2014 12:47 |
Last Modified: | 28 Jan 2014 12:47 |
URI: | http://real.mtak.hu/id/eprint/9310 |
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