title: Vitamin D deficiency-induced hypertension is associated with vascular oxidative stress and altered heart gene expression.
abstract: Vitamin D deficiency (VDD) is associated with an increased cardiovascular risk. We investigated the effect of VDD on the cardiovascular system of growing male rats fed with a vitamin D-deficient diet. Using isolated rat aorta, we assessed both superoxide anion and endothelial-dependent relaxations. Microarray technology was used to identify changes induced by VDD in cardiac gene expression. Compared with control, VDD increased systolic blood pressure (P < 0.05) and superoxide anion production in the aortic wall (P < 0.05) and tended to increase serum levels of angiotensin II and atrial natriuretic peptide (P < 0.15). However, VDD slightly improved maximal relaxation to acetylcholine from 75 % ± 3% to 83% ± 2% (P < 0.05). Incubation of aortic rings either with nitro-l-arginine methyl ester (l-NAME) or catalase did not eliminate the enhancement of endothelial-mediated relaxation observed in vitamin D-deficient rats. Only incubation with indometacin or calcium-activated potassium channels blockers suppressed this difference. Compared with control, the expression of 51 genes showed different expression, including several genes involved in the regulation of oxidative stress and myocardial hypertrophy. In conclusion, VDD in early life increases arterial blood pressure, promotes vascular oxidative stress, and induces changes in cardiac gene expression. However, the endothelial-mediated regulation of vasomotor tone is maintained throughout the enhancement of an NO-independent compensatory pathway.
authors.affiliation: Department of Cardiology, Université Libre de Bruxelles (ULB), Brussels, Belgium. jfxa@skynet.be
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Argacha
authors.forename: Dominique
authors.initials: D
authors.lastname: Egrise
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Pochet
authors.forename: David
authors.initials: D
authors.lastname: Fontaine
authors.forename: Anne
authors.initials: A
authors.lastname: Lefort
authors.forename: Frédérick
authors.initials: F
authors.lastname: Libert
authors.forename: Serge
authors.initials: S
authors.lastname: Goldman
authors.forename: Philippe
authors.initials: P
authors.lastname: van de Borne
authors.forename: Guy
authors.initials: G
authors.lastname: Berkenboom
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Moreno-Reyes
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D004730:Endothelium, Vascular / Q000503:physiopathology; D005786:Gene Expression Regulation; D006973:Hypertension / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014808:Vitamin D Deficiency / Q000150:complications* / Q000235:genetics / Q000378:metabolism