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

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 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; AT2expression 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 AT1rather 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.