Full metadata record
DC Field | Value | Language |
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dc.creator | Fortuño, A. (Ana) | - |
dc.creator | Bidegain, J. (J.) | - |
dc.creator | Robador, P.A. (Pablo A.) | - |
dc.creator | Hermida, J. (José) | - |
dc.creator | Lopez-Sagaseta, J. (Jacinto) | - |
dc.creator | Beloqui, O. (Óscar) | - |
dc.creator | Diez-Martinez, J. (Javier) | - |
dc.creator | Zalba, G. (Guillermo) | - |
dc.date.accessioned | 2011-06-13T11:59:35Z | - |
dc.date.available | 2011-06-13T11:59:35Z | - |
dc.date.issued | 2009 | - |
dc.identifier.citation | Fortuño A, Bidegain J, Robador PA, Hermida J, Lopez-Sagaseta J, Beloqui O, et al. Losartan metabolite EXP3179 blocks NADPH oxidase-mediated superoxide production by inhibiting protein kinase C: potential clinical implications in hypertension. Hypertension 2009 Oct;54(4):744-750. | es_ES |
dc.identifier.issn | 1524-4563 | - |
dc.identifier.uri | https://hdl.handle.net/10171/18527 | - |
dc.description.abstract | Oxidative stress plays a critical role in the pathogenesis of hypertension. The NADPH oxidase constitutes a major source of superoxide anion in phagocytic cells, and its activation is associated with matrix metalloproteinase (MMP)-9 secretion by these cells. We investigated the effects of the angiotensin II type 1 receptor antagonist losartan and its metabolites (EXP3174 and EXP3179) on NADPH oxidase activity and MMP-9 secretion in human phagocytic cells. EXP3179, but not losartan and EXP3174, dose-dependently inhibited (P<0.05) phorbol myristate acetate and insulin-stimulated NADPH oxidase activity. EXP3179 also inhibited phorbol myristate acetate-induced NADPH oxidase in endothelial cells. In addition, EXP3179 inhibited (P<0.05) both phorbol myristate acetate-stimulated p47phox translocation from cytosol to membranes and protein kinase C activity. Affinity experiments and enzymatic assays confirmed that EXP3179 inhibited several protein kinase C isoforms. EXP3179 also inhibited (P<0.05) phorbol myristate acetate-stimulated MMP-9 secretion. In a study performed in 153 hypertensive patients, phagocytic NADPH oxidase activity was lower (P<0.05) in losartan-treated compared with untreated patients and in patients treated with other angiotensin II type 1 receptor antagonists or with angiotensin-converting enzyme inhibitors. Plasma levels of MMP-9 were lower (P<0.05) in losartan-treated hypertensives compared with the other group of patients. Thus, EXP3179 acts as a blocker of the NADPH oxidase in phagocytic cells by a potential mechanism that targets the protein kinase C signaling pathway. This effect can be involved in reduced MMP-9 secretion by these cells. It is proposed that the EXP3179 metabolite may confer to losartan the specific capacity to reduce oxidative stress mediated by phagocytic cells in hypertensive patients. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Heart Association | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | EXP3179 | es_ES |
dc.subject | Hypertension | es_ES |
dc.subject | Losartan | es_ES |
dc.subject | Metalloproteinases | es_ES |
dc.subject | NADPH oxidase | es_ES |
dc.subject | PKC | es_ES |
dc.title | Losartan metabolite EXP3179 blocks NADPH oxidase-mediated superoxide production by inhibiting protein kinase C: potential clinical implications in hypertension | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publisherversion | http://hyper.ahajournals.org/cgi/content/abstract/54/4/744 | es_ES |
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