Changes in angiotensin receptors expression play a pivotal role in the renal damage observed in spontaneously hypertensive rats

Am J Physiol Renal Physiol. 2011 Feb;300(2):F499-510. doi: 10.1152/ajprenal.00384.2010. Epub 2010 Nov 17.

Abstract

The renal renin-angiotensin system plays a central role in the development of hypertension. The aim of this work was to verify the expression of angiotensin II receptors AT(1)R and AT(2)R in the microsomal fraction of renal cortex and correlate this with the development of hypertension and renal damage in spontaneously hypertensive rats (SHR) using Wistar-Kyoto rats (WKY) as controls. AT(1)R expression increased (126%) and AT(2)R expression decreased (66%) in 4-wk-old SHR; AT(2) expression decreased in 14-wk-old SHR (61%) compared with respective age-matched WKY. These modifications were correlated to the increase in protein kinase C activity and decrease in protein kinase A activity. Four-week-old SHR showed large accumulations of macrophages in kidney glomerulus and the tubulointerstitial area, dense cortical collagen deposition, and arterial proliferative changes in the walls of arterioles and medium-sized vessels. Similar modifications were also observed in 14-wk-old SHR. Four-week-old SHR treated with losartan (30 mg·kg(-1)·day(-1)) or hydralazine (15 and 30 mg·kg(-1)·day(-1)) by gavage for 10 wk did not develop hypertension. The decrease in AT(2)R expression and renal damage observed in SHR remained even after treatment with hydralazine. On the other hand, losartan treatment prevented the modifications observed in 14-wk-old SHR, indicating that renal injuries are caused specifically by AT(1) rather than an increase in blood pressure. Our results indicate that the imbalance in AT(1)R and AT(2)R expression is associated with an inflammatory process that contributes to renal injury in adult SHR and to the development of hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Arterioles / drug effects
  • Arterioles / metabolism
  • Collagen / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Gene Expression / drug effects
  • Hydralazine / pharmacology
  • Hypertension / genetics
  • Hypertension / metabolism*
  • Kidney Diseases / drug therapy
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism
  • Losartan / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Protein Kinase C / metabolism
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptor, Angiotensin, Type 1 / metabolism*
  • Receptor, Angiotensin, Type 2 / metabolism*
  • Renin-Angiotensin System / drug effects

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Hydralazine
  • Collagen
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Losartan