Calcitriol supplementation improves endothelium-dependent vasodilation in rat hypertensive renal injury

Kidney Blood Press Res. 2014;39(1):17-27. doi: 10.1159/000355773. Epub 2014 Apr 30.

Abstract

Background/aims: Vitamin D increases renal expression of klotho in normotensive rats. Klotho reduces oxidative stress.

Methods: In this study, we aimed to determine if vitamin D would suppress oxidative stress using 4 groups of hypertensive rats: uninephrectomized, stroke-prone, spontaneously hypertensive rats fed a high-salt (6%) diet (controls; C); those treated with irbesartan (I); those treated with calcitriol (V); and those treated with both irbesartan and calcitriol (I+V).

Results: Systolic blood pressure was higher in the C group than in the I and I+V groups. Albuminuria was attenuated in groups I, V, and I+V. Renal angiotensin II (AngII) concentration was lower in groups I and I+V than in group C, and plasma AngII levels of groups I and V were higher and lower than those in group C, respectively. Compared with group C, renal klotho expression, 8-epi-prostaglandin F2α excretion, and acetylcholine-induced decrease in blood pressure improved in the V and I+V groups.

Conclusions: The data indicate that irbesartan effectively decreases blood pressure and renal AngII levels, and improves albuminuria. Our findings indicate that vitamin D enhances klotho expression, suppressing oxidative stress and albuminuria without substantial changes in renal AngII levels. These results suggest that the amelioration of endothelium function by vitamin D involves free klotho.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism
  • Animals
  • Antihypertensive Agents / pharmacology
  • Biphenyl Compounds / pharmacology
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Calcitriol / administration & dosage
  • Calcitriol / pharmacology*
  • Dietary Supplements*
  • Dinoprost / analogs & derivatives
  • Dinoprost / metabolism
  • Disease Models, Animal
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Glucuronidase / metabolism
  • Hypertension / complications
  • Hypertension / physiopathology*
  • Irbesartan
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney Diseases / etiology
  • Kidney Diseases / physiopathology*
  • Klotho Proteins
  • Male
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Rats
  • Rats, Inbred SHR
  • Tetrazoles / pharmacology
  • Vasodilation / drug effects*
  • Vasodilation / physiology
  • Vitamins / administration & dosage
  • Vitamins / pharmacology*

Substances

  • Antihypertensive Agents
  • Biphenyl Compounds
  • Tetrazoles
  • Vitamins
  • Angiotensin II
  • 8-epi-prostaglandin F2alpha
  • Dinoprost
  • Glucuronidase
  • Klotho Proteins
  • Calcitriol
  • Irbesartan