Battle against the renin-angiotensin system: help from an unexpected party

Abstract

1,25 Dihydroxyvitamin D3 is a key player in calcium and phosphorus homeostasis and bone formation, and disturbances in this system cause deleterious clinical effects. Besides these actions, there is accumulating evidence for nonclassical actions of 1,25(OH)2D3 and its analogues such as immunomodulation and antiproliferation. Low levels of 1,25(OH)2D3 in the circulation are associated with a high incidence of autoimmune diseases like multiple sclerosis. According to the data from in vitro experiments and animal models, vitamin D might diminish the proinflammatory immune response by enhancing regulatory T cell functionality [1]. An inverse association of circulating 25-OH vitamin D levels with blood pressure has been demonstrated, and likewise, it has been shown that the treatment with the vitamin D analogue alphacalcidiol reduces blood pressure [2,3]. Also, 1,25(OH)2D3 reduces plasma renin activity, angiotensin II (Ang II) and myocardial hypertrophy [4–6]. A murine model of vitamin D receptor (VDR) deficiency displays elevated renin mRNA and protein levels [7]. In 1α-hydroxylase knockout-mice, similar findings were found and the corresponding phenotype was rescued by the ACE inhibitor captopril and the Ang II type 1 blocker (ARB) losartan but not by a high calcium and phosphorus diet suggesting that these effects are independent [8]. In this light, a recent study investigated the combined effect of the ARB losartan and the non-calcaemic vitamin D analogue paricalcitol (19-nor-1,25-dihydroxyvitamin D2) on the development and progression of diabetic nephropathy [9]. Diabetic nephropathy is the most common cause of end-stage renal disease with an even increasing incidence throughout the western world [10]. Blockers of the