Activation of NAD(P)H: quinone oxidoreductase ameliorates spontaneous hypertension in an animal model via modulation of eNOS activity

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dc.contributor.authorYong Hoon Kim-
dc.contributor.authorJung Hwan Hwang-
dc.contributor.authorJung Ran Noh-
dc.contributor.authorGil Tae Gang-
dc.contributor.authorD H Kim-
dc.contributor.authorH Y Son-
dc.contributor.authorT H Kwak-
dc.contributor.authorM Shong-
dc.contributor.authorI K Lee-
dc.contributor.authorChul Ho Lee-
dc.date.accessioned2017-04-19T09:24:32Z-
dc.date.available2017-04-19T09:24:32Z-
dc.date.issued2011-
dc.identifier.issn0008-6363-
dc.identifier.uri10.1093/cvr/cvr110ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/10239-
dc.description.abstractAims Hypertension is one of the most common human diseases worldwide, and extensive research efforts are focused upon the identification and utilizing of novel therapeutic drug targets. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is an important regulator of blood pressure (BP). β-Lapachone (βL), a well-known substrate of NAD(P)H:quinone oxidoreductase (NQO1), increases the cellular NAD+/NADH ratio via the activation of NQO1. In this study, we evaluated whether βL-induced activation of NQO1 modulates BP in an animal model of hypertension. Methods and results Spontaneously hypertensive rats (SHR), primary human aortic endothelial cells (HAEC), and endothelial cell lines were used to investigate the hypotensive effect of βL and its mode of action. βL treatment stimulated endothelium-dependent vascular relaxation in response to acetylcholine in aorta of SHR and dramatically lowered BP in SHR, but the hypotensive effect was completely blocked by eNOS inhibition withnitro-l-arginine methyl ester. Aortic eNOS phosphorylation and eNOS protein expression were significantly increased in βL-treated SHR. In vitro studies revealed that βL treatment elevated the intracellular NAD+/NADH ratio and concentration of free Ca2+ ([Ca2+]i), and resulted in Akt/AMP-activated protein kinase/eNOS activation. These effects were abolished by NQO1 siRNA and [Ca2+]i inhibition through a ryanodine receptor blockade. Conclusion This study is the first to demonstrate that NQO1 activation has a hypotensive effect mediated by eNOS activation via cellular NAD+/NADH ratio modulation in an animal model. These results provide strong evidence suggesting NQO1 might be a new therapeutic target for hypertension.-
dc.publisherOxford Univ Press-
dc.titleActivation of NAD(P)H: quinone oxidoreductase ameliorates spontaneous hypertension in an animal model via modulation of eNOS activity-
dc.title.alternativeActivation of NAD(P)H: quinone oxidoreductase ameliorates spontaneous hypertension in an animal model via modulation of eNOS activity-
dc.typeArticle-
dc.citation.titleCardiovascular Research-
dc.citation.number3-
dc.citation.endPage527-
dc.citation.startPage519-
dc.citation.volume91-
dc.contributor.affiliatedAuthorYong Hoon Kim-
dc.contributor.affiliatedAuthorJung Hwan Hwang-
dc.contributor.affiliatedAuthorJung Ran Noh-
dc.contributor.affiliatedAuthorGil Tae Gang-
dc.contributor.affiliatedAuthorChul Ho Lee-
dc.contributor.alternativeName김용훈-
dc.contributor.alternativeName황정환-
dc.contributor.alternativeName노정란-
dc.contributor.alternativeName강길태-
dc.contributor.alternativeName김도형-
dc.contributor.alternativeName손화영-
dc.contributor.alternativeName곽태환-
dc.contributor.alternativeName송민호-
dc.contributor.alternativeName이인규-
dc.contributor.alternativeName이철호-
dc.identifier.bibliographicCitationCardiovascular Research, vol. 91, no. 3, pp. 519-527-
dc.identifier.doi10.1093/cvr/cvr110-
dc.subject.keywordβ-Lapachone-
dc.subject.keywordeNOS-
dc.subject.keywordHypertension-
dc.subject.keywordNAD+/NADH ratio-
dc.subject.keywordNQO1-
dc.subject.localβ-lapachone-
dc.subject.localβ-Lapachone-
dc.subject.localeNOS-
dc.subject.localENOS-
dc.subject.localHypertension-
dc.subject.localhypertension-
dc.subject.localNAD+/NADH ratio-
dc.subject.localNQO1-
dc.description.journalClassY-
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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