Genetic deletion of the angiotensin-(1-7) receptor Mas leads to glomerular hyperfiltration and microalbuminuria

Kidney Int. 2009 Jun;75(11):1184-1193. doi: 10.1038/ki.2009.61. Epub 2009 Mar 4.

Abstract

Angiotensin-(1-7), an active fragment of both angiotensins I and II, generally opposes the vascular and proliferative actions of angiotensin II. Here we evaluated effects of the angiotensin-(1-7) receptor Mas on renal physiology and morphology using Mas-knockout mice. Compared to the wild-type animals, Mas knockout mice had significant reductions in urine volume and fractional sodium excretion without any significant change in free-water clearance. A significantly higher inulin clearance and microalbuminuria concomitant with a reduced renal blood flow suggest that glomerular hyperfiltration occurs in the knockout mice. Histological analysis found reduced glomerular tuft diameter and increased expression of collagen IV and fibronectin in the both the mesangium and interstitium, along with increased collagen III in the interstitium. These fibrogenic changes and the renal dysfunction of the knockout mice were associated with an upregulation of angiotensin II AT1 receptor and transforming growth factor-beta mRNA. Our study suggests that Mas acts as a critical regulator of renal fibrogenesis by controlling effects transduced through angiotensin II AT1 receptors in the kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albuminuria / etiology*
  • Albuminuria / genetics
  • Animals
  • Collagen / biosynthesis
  • Fibronectins / biosynthesis
  • Fibrosis
  • Gene Deletion*
  • Glomerular Filtration Rate
  • Kidney Glomerulus / physiopathology*
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics*
  • Receptor, Angiotensin, Type 1 / biosynthesis
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptors, G-Protein-Coupled / deficiency
  • Receptors, G-Protein-Coupled / genetics*
  • Up-Regulation

Substances

  • Fibronectins
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Receptor, Angiotensin, Type 1
  • Receptors, G-Protein-Coupled
  • Collagen