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Article: Chronic treatment with vitamin D lowers arterial blood pressure and reduces endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat

TitleChronic treatment with vitamin D lowers arterial blood pressure and reduces endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat
Authors
Issue Date2010
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, 2010, v. 299 n. 4, p. H1226-H1234 How to Cite?
AbstractVitamin D has cardiovascular protective effects besides regulating calcium homeostasis. To examine the chronic in vivo effect of a physiological dose of 1,25-dihydroxyvitamin D3 on the occurrence of endothelium-dependent contractions, spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were treated with the vitamin D derivative for 6 wk. The serum 1,25-dihydroxyvitamin D3 level of both treated WKY and SHR was significantly higher than in untreated rats while the mean arterial blood pressure of the treated SHR was significantly lower than that of control SHR. Aortic rings with or without endothelium were studied in conventional organ chambers for isometric force measurement. Confocal microscopy was used to measure the cytosolic free calcium concentration (with the fluorescent dye fluo 4) and reactive oxygen species (ROS; with dichlorodihydrofluorescein diacetate). Reverse transcription PCR and Western blotting were used to determine the mRNA and protein expression level of cyclooxygenase-1 (COX-1), prostacyclin synthase, and thromboxane synthase. The endothelium-dependent concentration-contraction curves to both acetylcholine- and A-23187-induced contractions were shifted to the right in aortas from treated SHR but not from treated WKY. The chronic treatment normalized the relaxations of contracted preparations to acetylcholine. There were no significant differences in the increases in cytosolic free calcium concentration evoked by acetylcholine and A-23187 between control and treated groups. The endothelial ROS level was higher in SHR than WKY aortas and reduced by the chronic treatment. The gene and protein expression studies indicated that the overexpression of COX-1 observed in SHR aorta was reduced by the chronic treatment. These results demonstrate that chronic treatment with 1,25-dihydroxyvitamin D3 modulates vascular tone and this modulation is accompanied by a lowered blood pressure, reduced expression of COX-1 mRNA and protein, and reduced ROS level in SHR. The reduction in endothelium-dependent contractions does not involve the surge in endothelial cytosolic calcium concentration that initiates the contractions. Copyright © 2010 the American Physiological Society.
Persistent Identifierhttp://hdl.handle.net/10722/171407
ISSN
2015 Impact Factor: 3.324
2015 SCImago Journal Rankings: 1.823
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, MSKen_US
dc.contributor.authorDelansorne, Ren_US
dc.contributor.authorMan, RYKen_US
dc.contributor.authorSvenningsen, Pen_US
dc.contributor.authorVanhoutte, PMen_US
dc.date.accessioned2012-10-30T06:13:57Z-
dc.date.available2012-10-30T06:13:57Z-
dc.date.issued2010en_US
dc.identifier.citationAmerican Journal Of Physiology - Heart And Circulatory Physiology, 2010, v. 299 n. 4, p. H1226-H1234en_US
dc.identifier.issn0363-6135en_US
dc.identifier.urihttp://hdl.handle.net/10722/171407-
dc.description.abstractVitamin D has cardiovascular protective effects besides regulating calcium homeostasis. To examine the chronic in vivo effect of a physiological dose of 1,25-dihydroxyvitamin D3 on the occurrence of endothelium-dependent contractions, spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were treated with the vitamin D derivative for 6 wk. The serum 1,25-dihydroxyvitamin D3 level of both treated WKY and SHR was significantly higher than in untreated rats while the mean arterial blood pressure of the treated SHR was significantly lower than that of control SHR. Aortic rings with or without endothelium were studied in conventional organ chambers for isometric force measurement. Confocal microscopy was used to measure the cytosolic free calcium concentration (with the fluorescent dye fluo 4) and reactive oxygen species (ROS; with dichlorodihydrofluorescein diacetate). Reverse transcription PCR and Western blotting were used to determine the mRNA and protein expression level of cyclooxygenase-1 (COX-1), prostacyclin synthase, and thromboxane synthase. The endothelium-dependent concentration-contraction curves to both acetylcholine- and A-23187-induced contractions were shifted to the right in aortas from treated SHR but not from treated WKY. The chronic treatment normalized the relaxations of contracted preparations to acetylcholine. There were no significant differences in the increases in cytosolic free calcium concentration evoked by acetylcholine and A-23187 between control and treated groups. The endothelial ROS level was higher in SHR than WKY aortas and reduced by the chronic treatment. The gene and protein expression studies indicated that the overexpression of COX-1 observed in SHR aorta was reduced by the chronic treatment. These results demonstrate that chronic treatment with 1,25-dihydroxyvitamin D3 modulates vascular tone and this modulation is accompanied by a lowered blood pressure, reduced expression of COX-1 mRNA and protein, and reduced ROS level in SHR. The reduction in endothelium-dependent contractions does not involve the surge in endothelial cytosolic calcium concentration that initiates the contractions. Copyright © 2010 the American Physiological Society.en_US
dc.languageengen_US
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/en_US
dc.relation.ispartofAmerican Journal of Physiology - Heart and Circulatory Physiologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAorta - Drug Effects - Metabolism - Physiopathologyen_US
dc.subject.meshBlood Pressure - Drug Effects - Physiologyen_US
dc.subject.meshCalcitriol - Blooden_US
dc.subject.meshCalcium - Metabolismen_US
dc.subject.meshCyclooxygenase 1 - Metabolismen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshEndothelium, Vascular - Drug Effects - Metabolism - Physiopathologyen_US
dc.subject.meshHypertension - Physiopathologyen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Inbred Shren_US
dc.subject.meshRats, Inbred Wkyen_US
dc.subject.meshReactive Oxygen Species - Metabolismen_US
dc.subject.meshVasoconstriction - Drug Effects - Physiologyen_US
dc.subject.meshVitamin D - Pharmacologyen_US
dc.titleChronic treatment with vitamin D lowers arterial blood pressure and reduces endothelium-dependent contractions in the aorta of the spontaneously hypertensive raten_US
dc.typeArticleen_US
dc.identifier.emailMan, RYK:rykman@hkucc.hku.hken_US
dc.identifier.emailVanhoutte, PM:vanhoutt@hku.hken_US
dc.identifier.authorityMan, RYK=rp00236en_US
dc.identifier.authorityVanhoutte, PM=rp00238en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1152/ajpheart.00288.2010en_US
dc.identifier.pmid20693391-
dc.identifier.scopuseid_2-s2.0-77958035114en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77958035114&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume299en_US
dc.identifier.issue4en_US
dc.identifier.spageH1226en_US
dc.identifier.epageH1234en_US
dc.identifier.isiWOS:000283857300029-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWong, MSK=23483301500en_US
dc.identifier.scopusauthoridDelansorne, R=6603092593en_US
dc.identifier.scopusauthoridMan, RYK=7004986435en_US
dc.identifier.scopusauthoridSvenningsen, P=8941796400en_US
dc.identifier.scopusauthoridVanhoutte, PM=7202304247en_US
dc.identifier.citeulike7677426-

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