title: Vitamin D insufficiency is associated with impaired vascular endothelial and smooth muscle function and hypertension in young rats.
abstract: Increasing evidence links vitamin D deficiency and cardiovascular dysfunction in human adults. There is a worldwide increase in the prevalence of vitamin D deficiency in women of reproductive age, particularly dark-skinned and/or veiled women and their infants. We used a rat model to determine the functional impact of vitamin D deficiency during intra uterine and early life on resistance artery reactivity and blood pressure in the offspring as young adults. Rat dams were maintained on vitamin D deficient or replete chow before and during pregnancy and lactation. The offspring were maintained on the same chow until studied at 7-8 weeks of age. Conscious blood pressure was measured. Endothelial and smooth muscle function were tested in mesenteric arteries on a pressure myograph. Vitamin D deficient male and female offspring had a 10-fold lower serum 25-hydroxyvitamin D (P < 0.0001) and markedly elevated blood pressures (11-20 mmHg, P < 0.001) and heart rates (21-40 beats min(-1), P < 0.02) than control fed offspring. Serum calcium was unchanged. Mesenteric artery myogenic tone was doubled in vitamin D deficiency. Endothelium-derived nitric oxide-evoked dilation was halved in arteries from vitamin D deficient males and dioestrous females. Dilation attributed to endothelium-derived hyperpolarizing factor was all but abolished in vitamin D deficient oestrous females. Nitroprusside-evoked dilation was unaltered in arteries from males, but was markedly reduced in vessels of vitamin D deplete females. In conclusion, early life vitamin D deficiency is associated with endothelial vasodilator dysfunction, and this is likely to contribute to the accompanying elevation in blood pressure and an increased cardiovascular disease risk.
authors.affiliation: Department of Physiology, Monash University, Victoria 3800, Australia.
authors.forename: Marianne
authors.initials: M
authors.lastname: Tare
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Emmett
authors.forename: Harold A
authors.initials: HA
authors.lastname: Coleman
authors.forename: Con
authors.initials: C
authors.lastname: Skordilis
authors.forename: Darryl W
authors.initials: DW
authors.lastname: Eyles
authors.forename: Ruth
authors.initials: R
authors.lastname: Morley
authors.forename: Helena C
authors.initials: HC
authors.lastname: Parkington
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D001685:Biological Factors; D011453:Prostaglandins; C067410:endothelium-dependent hyperpolarization factor; D014807:Vitamin D; D009599:Nitroprusside; D009569:Nitric Oxide; C104450:25-hydroxyvitamin D