Calcitriol reduces kidney development disorders in rats provoked by losartan administration during lactation

Sci Rep. 2017 Sep 13;7(1):11472. doi: 10.1038/s41598-017-11815-8.

Abstract

Calcitriol has important effects on cellular differentiation and proliferation, as well as on the regulation of the renin gene. Disturbances in renal development can be observed in rats exposed to angiotensin II (AngII) antagonists during lactation period. The lack of tubular differentiation in losartan-treated rats can affect calcitriol uptake. This study evaluated the effect of calcitriol administration in renal development disturbances in rats provoked by losartan (AngII type 1 receptor antagonist) administration during lactation. Animals exposed to losartan presented higher albuminuria, systolic blood pressure, increased sodium and potassium fractional excretion, and decreased glomerular filtration rate compared to controls. These animals also showed a decreased glomerular area and a higher interstitial relative area from the renal cortex, with increased expression of fibronectin, alpha-SM-actin, vimentin, and p-JNK; and an increased number of macrophages, p-p38, PCNA and decreased cubilin expression. Increased urinary excretion of MCP-1 and TGF-β was also observed. All these alterations were less intense in the losartan + calcitriol group.The animals treated with calcitriol showed an improvement in cellular differentiation, and in renal function and structure. This effect was associated with reduction of cell proliferation and inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Biopsy
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Breast Feeding
  • Calcitriol / pharmacology*
  • Chemokine CCL2 / urine
  • Congenital Abnormalities / drug therapy*
  • Congenital Abnormalities / etiology
  • Congenital Abnormalities / pathology*
  • Congenital Abnormalities / physiopathology
  • Disease Models, Animal
  • Female
  • Immunohistochemistry
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / etiology
  • Kidney Diseases / pathology*
  • Kidney Diseases / physiopathology
  • Kidney Function Tests
  • Lactation*
  • Losartan / administration & dosage*
  • Male
  • Rats
  • Transforming Growth Factor beta / urine

Substances

  • Biomarkers
  • Ccl2 protein, rat
  • Chemokine CCL2
  • Transforming Growth Factor beta
  • Calcitriol
  • Losartan