Higher renal AT1 receptor affinity exaggerates Ang II induced Na/K‐ATPase stimulation in spontaneously hypertensive rats.

Abstract

Angiotensin II (Ang II) via renal Ang II type 1 receptors (AT1 R) regulates proximal tubular Na reabsorption by acting on Na/K‐ATPase (NKA) and thus plays an important role in regulation of blood pressure (BP). Recent evidences suggest that oxidative stress modulates the function of renal AT1 R during hypertension. The aim of the present study is to investigate if oxidative stress modulates renal AT1 R signaling in spontaneously hypertensive rats (SHR). We performed experiments in 12 weeks old SHR and Wistar Kyoto (WKY) rats served as control. Our results show that in addition to increased BP there is oxidative stress in proximal tubules, as evidenced by increase in protein carbonylation, in SHR compared to WKY rats. Western blot analysis showed equal AT1 R protein expression in SHR and WKY rats. 125I‐sar‐ANG II binding showed an increase in affinity of AT1 R in SHR, but no change in receptor numbers. In SHR there was enhanced AT1R‐ G protein‐coupling and stimulation of protein kinase C activity. In WKY rats, incubation of proximal tubules with Ang II caused stimulation of NKA at low (10−10M) concentration but not at high (10−6M) concentration. However in SHR we observed stimulation of NKA at both concentrations of Ang II.These data suggest that in SHR oxidative stress is associated with increased renal AT1 R affinity which leads to enhanced Ang II signaling resulting in greater NKA stimulation which contributes to hypertension.