Enhanced Angiotensin II-Induced Activation of Na⁺, K⁺-ATPase in the Proximal Tubules of Obese Zucker Rats

Abstract

Renal angiotensin II (AII) is suggested to play a role in the enhanced sodium reabsorption that causes a shift in pressure natriuresis in obesity related hypertension; however, the mechanism is not known. Therefore, to assess the influence of AII on tubular sodium transport, we determined the effect of AII on the Na⁺, K⁺-ATPase activity (NKA), an active transporter regulated by the AT₁ receptor activity, in the isolated proximal tubules of lean and obese Zucker rats. Also, we determined the levels of the tubular AT₁ receptor and associated signal transducing G proteins, as the initial signaling components that mediate the effects of AII on Na⁺, K⁺-ATPase activity. In the isolated proximal tubules, AII produced greater stimulation of the NKA activity in obese compared with lean rats. Determination of the AT₁ receptors by Scatchard analysis of the [¹²⁵I] Sar-Ang II binding and Western blot analysis in the basolateral (BLM) and brush border membrane (BBM) revealed a modest but significant increase (23%) in the AT₁ receptor number mainly in the BLM of obese compared with lean rats. The AII affinity for AT₁ receptors, as determined by IC₅₀ values of AII to displace [¹²⁵I] Sar-Ang II binding in BLM and BBM were similar in lean and obese rats. Western blot analysis revealed significant increases in Giα₁, Giα₂, Giα₃, and Gq/₁₁α in BLM and Giα₁, Giα₃, and Gq/₁₁α in BBM of obese as compared with lean rats. The increase in the levels of the AT₁ receptor and G proteins, mainly in the BLM, may be contributing to the enhanced AII-induced activation of NKA in the proximal tubules of obese rats. This phenomenon, in part, may be responsible for the increased sodium reabsorption and the development of hypertension in obese Zucker rats.

Keywords:

• AT₁ receptor
• G-proteins
• hypertension
• kidney
• sodium pump