Abstract 298: Vitamin D3 Supplementation in Obesity Corrects the Renal Vascular Response to Angiotensin II Akin to the Action of a Converting Enzyme Inhibitor
Background: Increased activity of the renal-vascular renin-angiotensin system (RAS) is a leading mechanism for chronic kidney disease (CKD) in obesity. Low vitamin D levels are associated with increased RAS activity, obesity, and the development of CKD; we hypothesized that vitamin D3 therapy in obesity would lower renal-vascular RAS activity and thus increase the renal-vascular sensitivity to angiotensin II (AngII) akin to an ACE inhibitor.
Methods: 14 morbidly obese subjects (BMI 36 kg/m2) with hypertension, pre-diabetes, 25(OH)D<25 ng/mL, and normal renal function were studied. Anti-hypertensive medications were withdrawn for up to 3 months, and subjects completed a controlled sodium diet for 1 week prior to study visits, which occurred before and after 15,000 IU/daily of vitamin D3 for 1 month. At each study visit, renal plasma flow (RPF, via p-aminohippurate clearance) was measured during an infusion of AngII (1 ng/kg/min) in triplicate at baseline, 45, and 90 mins. Subjects were then treated with captopril and underwent a second infusion of AngII to evaluate the change in renal-vascular RAS induced by captopril. Repeated-measures regression analyses were used to examine the effect of vitamin D3 therapy on RPF while accounting for variation in PAH measurements and the lack of independence between intra-individual observations.
Results: With vitamin D3 therapy, mean 25(OH)D rose from 18 to 52 ng/mL, PTH fell from 46 to 37 pg/mL, and baseline RPF rose from 383.6 to 401.0 mL/min/1.73m2 (P<0.01). Vitamin D3 intervention modified the influence of AngII infusion on RPF; there was a greater decline in RPF (P<0.05) following vitamin D3 therapy, suggesting a reduction in renal-vascular RAS. After a dose of captopril, the renal-vascular sensitivity to AngII was significantly augmented at both study visits, but this improvement was much smaller following vitamin D3 therapy (P<0.05); raising vitamin D levels corrected the renal-vascular sensitivity to AngII similarly to ACE inhibition.
Conclusions: In this controlled physiology study, vitamin D3 therapy in obese hypertensives increased basal RPF and the renal-vascular sensitivity to AngII akin to the effect of an ACE inhibitor. Chronic vitamin D3 therapy in obesity may reduce the risk of CKD by reducing RAS activity.
- © 2012 by American Heart Association, Inc.