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

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 AT₁R and AT₂R 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. AT1R expression increased (126%) and AT₂R expression decreased (66%) in 4-wk-old SHR; AT₂ 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 AT₂R 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 AT₁ rather than an increase in blood pressure. Our results indicate that the imbalance in AT₁R and AT₂R expression is associated with an inflammatory process that contributes to renal injury in adult SHR and to the development of hypertension. [ABSTRACT FROM AUTHOR]