Vitamin D3 Therapy Corrects the Tissue Sensitivity to Angiotensin II Akin to the Action of a Converting Enzyme Inhibitor in Obese Hypertensives: An Interventional Study

Abstract

Abstract Context: Vitamin D deficiency and obesity are associated with increased tissue renin-angiotensin system (RAS) activity. Objective: The objective of the study was to evaluate whether vitamin D3 therapy in obesity reduces tissue-RAS activity, as indicated by an increase in tissue sensitivity to angiotensin II (AngII). Participants: Participants included obese subjects with hypertension and 25-hydroxyvitamin D less than 25 ng/ml. Design: Subjects were studied before and after 1 month of vitamin D3 15,000 IU/d, while in dietary sodium balance, and off all interfering medications. Fourteen subjects successfully completed all study procedures. Setting: The study was conducted at a clinical research center. Outcome Measures: At each study visit, tissue sensitivity to AngII was assessed by measuring renal plasma flow (RPF), mean arterial pressure (MAP), and adrenal secretion of aldosterone during an infusion of AngII. Subjects were then given captopril, and a second AngII infusion to evaluate the effect of captopril on tissue-RAS activity. Results: Vitamin D3 therapy increased 25-hydroxyvitamin D (18 to 52 ng/ml) and basal RPF (+5%) and lowered supine MAP (−3%) (all P < 0.01). There was a greater decline in RPF and higher stimulation of aldosterone with AngII infusion after vitamin D3 therapy (both P < 0.05). As anticipated, captopril increased the renal-vascular, MAP, and adrenal sensitivity to AngII, but this effect was much smaller after vitamin D3 therapy, indicating that vitamin D3 therapy corrected the tissue sensitivity to AngII akin to captopril. Conclusions: Vitamin D3 therapy in obese hypertensives modified RPF, MAP, and tissue sensitivity to AngII similar to converting enzyme inhibition. Whether chronic vitamin D3 therapy abrogates the development of diseases associated with excess RAS activity warrants investigation.