Abstract
Endothelial dysfunction and vitamin D deficiency are prevalent in patients with cardiovascular disease (CVD) and chronic kidney disease (CKD). Both are risk factors for cardiovascular events in patients with CKD. No studies have investigated the effect of nutritional forms of vitamin D on endothelial function in earlier stages of CKD, when vascular endothelium may be more amenable to this therapy. We studied the effect of ergocalciferol in a pre-clinical model of mild uraemia.Male Wistar rats underwent either a 5/6th nephrectomy or sham surgery. Four weeks after the final stage of the surgery, these two groups were randomly allocated to placebo or an oral dose of 1000 iu of ergocalcfierol at day 7 and 2 pre sacrifice. Vascular responses to acetylcholine, Spermine NONOate and phenylephrine were determined in aortic rings. Blood pressure, calcium, phosphate and parathyroid hormone were measured in all groups.Ergocalciferol significantly improved the endothelium-dependent responses to acetylcholine and overcame the blunting of the contractile response to phenylephrine seen in uraemic animals. Ergocalciferol improved the contractile response to potassium chloride in uraemic, but not sham animals. All effects occurred independently of changes to calcium, phosphate, parathyroid hormone and systolic blood pressure. There were no differences in endothelium-independent relaxation to Spermine NONOate.In summary, in a model of mild uraemia, ergocalciferol improved vasodilator and vasoconstrictor tone independently of blood pressure and bone mineral parameters suggesting a direct effect of ergocalciferol on the endothelium.
Highlights
Chronic kidney disease (CKD) and concomitant vitamin D deficiency (VDD) is a common clinical entity that may result in an increased risk of cardiovascular disease (CVD) [1,2,3,4,5,6,7]
This study supports the use of ergocalciferol in patients with mild to moderate chronic kidney disease as a therapeutic adjunct to improve endothelial function and reduce cardiovascular disease, which remains the major cause of death in such patients
Summary
Chronic kidney disease (CKD) and concomitant vitamin D deficiency (VDD) is a common clinical entity that may result in an increased risk of cardiovascular disease (CVD) [1,2,3,4,5,6,7]. Progression to end-stage kidney disease (ESKD) in patients with CKD is far less common than death from CVD, the risk of which is increased even in mild CKD [9,10] and accounts for approximately 40% of all deaths in patients with ESKD [11,12]. Endothelial dysfunction is the consequence of a complex interplay of traditional and non-traditional risk factors and is strongly associated with an elevated risk of CVD in CKD alone and when CKD and VDD coexist [13,14,15,16]. We and others have demonstrated that therapeutic intervention with vitamin D has the potential to ameliorate endothelial dysfunction when CKD and VDD co-exist [17,18,19]
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