Abstract

Background: Many women of reproductive age are vitamin D (VitD) deficient and the implications for the cardiovascular health of their offspring are unknown. The aim of this study was to examine the effects of in utero and early life VitD insufficiency in rats on cardiovascular and renal function in the offspring. Methods: Female Sprague-Dawley rats were fed either a VitD-deplete or –replete diet before, and throughout pregnancy and lactation. Offspring were maintained on the same diet as their mothers until 3 months of age, after which time, all rats were fed VitD replete diet. Conscious arterial pressure was measured at 2 and 12 months of age. Vascular function was assessed using myography and real-time PCR was used to examine renal gene expression of elements of the renin-angiotensin system (RAS). Kidney function was measured by clearance methods. Results: At 3 days postnatal renal mRNA expression of renin was reduced in VitD deficient males but not females. At 2 months VitD deficient offspring had elevated mean arterial pressure (MAP) and heart rate (HR) compared with controls. Mesenteric arteries exhibited endothelial vasodilator dysfunction. Following long term VitD repletion, renal RAS gene expression, MAP, HR and endothelial function had normalised. However, renal arteries had enhanced responsiveness to angiotensin II and perivascular nerve stimulation, and renal glomerular filtration rate was reduced by 40% (P<0.002). Conclusions: Early life VitD insufficiency causes transient increases in MAP and changes in renal RAS and endothelial function, but causes permanent changes in renal artery constriction and kidney function.

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