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Article: Elevated pressure causes endothelial dysfunction in mouse carotid arteries by increasing local angiotensin signaling

TitleElevated pressure causes endothelial dysfunction in mouse carotid arteries by increasing local angiotensin signaling
Authors
Issue Date2015
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/
Citation
American Journal of Physiology: Heart and Circulatory Physiology, 2015, v. 308 n. 4, p. H358-H363 How to Cite?
AbstractExperiments were performed to determine whether or not acute exposure to elevated pressure would disrupt endothelium-dependent dilatation by increasing local angiotensin II (ANG II) signaling. Vasomotor responses of mouse-isolated carotid arteries were analyzed in a pressure myograph at a control transmural pressure (PTM) of 80 mmHg. Acetylcholine-induced dilatation was reduced by endothelial denudation or by inhibition of nitric oxide synthase (NG-nitro-L-arginine methyl ester, 100 μM). Transient exposure to elevated PTM (150 mmHg, 180 min) inhibited dilatation to acetylcholine but did not affect responses to the nitric oxide donor diethylamine NONOate. Elevated PTM also increased endothelial reactive oxygen species, and the pressure-induced endothelial dysfunction was prevented by the direct antioxidant and NADPH oxidase inhibitor apocynin (100 μM). The increase in endothelial reactive oxygen species in response to elevated PTM was reduced by the ANG II type 1 receptor (AT1R) antagonists losartan (3 μM) or valsartan (1 μM). Indeed, elevated PTM caused marked expression of angiotensinogen, the precursor of ANG II. Inhibition of ANG II signaling, by blocking angiotensin-converting enzyme (1 μM perindoprilat or 10 μM captopril) or blocking AT1Rs prevented the impaired response to acetylcholine in arteries exposed to 150 mmHg but did not affect dilatation to the muscarinic agonist in arteries maintained at 80 mmHg. After the inhibition of ANG II, elevated pressure no longer impaired endothelial dilatation. In arteries treated with perindoprilat to inhibit endogenous formation of the peptide, exogenous ANG II (0.3 μM, 180 min) inhibited dilatation to acetylcholine. Therefore, elevated pressure rapidly impairs endothelium-dependent dilatation by causing ANG expression and enabling ANG II-dependent activation of AT1Rs. These processes may contribute to the pathogenesis of hypertension-induced vascular dysfunction and organ injury. Copyright © 2015 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/211804
ISSN
2015 Impact Factor: 3.324
2015 SCImago Journal Rankings: 1.823
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorZhao, Y-
dc.contributor.authorFlavahan, S-
dc.contributor.authorLeung, SWS-
dc.contributor.authorXu, A-
dc.contributor.authorVanhoutte, PMGR-
dc.contributor.authorFlavahan, NA-
dc.date.accessioned2015-07-21T02:11:24Z-
dc.date.available2015-07-21T02:11:24Z-
dc.date.issued2015-
dc.identifier.citationAmerican Journal of Physiology: Heart and Circulatory Physiology, 2015, v. 308 n. 4, p. H358-H363-
dc.identifier.issn0363-6135-
dc.identifier.urihttp://hdl.handle.net/10722/211804-
dc.description.abstractExperiments were performed to determine whether or not acute exposure to elevated pressure would disrupt endothelium-dependent dilatation by increasing local angiotensin II (ANG II) signaling. Vasomotor responses of mouse-isolated carotid arteries were analyzed in a pressure myograph at a control transmural pressure (PTM) of 80 mmHg. Acetylcholine-induced dilatation was reduced by endothelial denudation or by inhibition of nitric oxide synthase (NG-nitro-L-arginine methyl ester, 100 μM). Transient exposure to elevated PTM (150 mmHg, 180 min) inhibited dilatation to acetylcholine but did not affect responses to the nitric oxide donor diethylamine NONOate. Elevated PTM also increased endothelial reactive oxygen species, and the pressure-induced endothelial dysfunction was prevented by the direct antioxidant and NADPH oxidase inhibitor apocynin (100 μM). The increase in endothelial reactive oxygen species in response to elevated PTM was reduced by the ANG II type 1 receptor (AT1R) antagonists losartan (3 μM) or valsartan (1 μM). Indeed, elevated PTM caused marked expression of angiotensinogen, the precursor of ANG II. Inhibition of ANG II signaling, by blocking angiotensin-converting enzyme (1 μM perindoprilat or 10 μM captopril) or blocking AT1Rs prevented the impaired response to acetylcholine in arteries exposed to 150 mmHg but did not affect dilatation to the muscarinic agonist in arteries maintained at 80 mmHg. After the inhibition of ANG II, elevated pressure no longer impaired endothelial dilatation. In arteries treated with perindoprilat to inhibit endogenous formation of the peptide, exogenous ANG II (0.3 μM, 180 min) inhibited dilatation to acetylcholine. Therefore, elevated pressure rapidly impairs endothelium-dependent dilatation by causing ANG expression and enabling ANG II-dependent activation of AT1Rs. These processes may contribute to the pathogenesis of hypertension-induced vascular dysfunction and organ injury. Copyright © 2015 the American Physiological Society.-
dc.languageeng-
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/-
dc.relation.ispartofAmerican Journal of Physiology: Heart and Circulatory Physiology-
dc.rightsAmerican Journal of Physiology: Heart and Circulatory Physiology. Copyright © American Physiological Society.-
dc.titleElevated pressure causes endothelial dysfunction in mouse carotid arteries by increasing local angiotensin signaling-
dc.typeArticle-
dc.identifier.emailLeung, SWS: swsleung@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.emailVanhoutte, PMGR: vanhoutt@hku.hk-
dc.identifier.authorityLeung, SWS=rp00235-
dc.identifier.authorityXu, A=rp00485-
dc.identifier.authorityVanhoutte, PMGR=rp00238-
dc.identifier.doi10.1152/ajpheart.00775.2014-
dc.identifier.pmid25485905-
dc.identifier.pmcidPMC4329479-
dc.identifier.hkuros244679-
dc.identifier.volume308-
dc.identifier.issue4-
dc.identifier.spageH358-
dc.identifier.epageH363-
dc.publisher.placeUnited States-

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