Increased Renal Angiotensin II AT1 Receptor Function in Obese Zucker Rat

Abstract

Angiotensin II (Ang II) via the activation of AT1 receptors and subsequent stimulation of the tubular sodium transporters increases sodium and water reabsorption in the proximal tubule. An enhanced tubular action of Ang II is implicated in obesity related hypertension; however, the mechanism of such a phenomenon is unknown. Present study was designed to determine the AT1 receptor numbers and function in the proximal tubule of obese and lean Zucker rats. Obese Zucker rats were hypertensive and hyperinsulinemic. The plasma renin activity was similar in the lean and obese rats. Angiotensin II stimulated the Na,H‐exchanger (NHE) activity in the proximal tubule, but the stimulatory response was markedly greater in obese than in lean rats. Similarly, Ang II caused greater inhibition in cAMP accumulation in the proximal tubule of obese compared to lean rats. The [125I]sar‐Ang II binding revealed a 100% increase in the AT1 receptor number in the brush border membrane (BBM) of obese compared to lean rats. The Western blot analysis revealed a 36–51% increase in the Giα1 and Giα3 in the BBM of obese compared to lean rats. We conclude that increases in the AT1 receptor number and abundance of the Giα on BBM may be responsible for the enhanced signaling and subsequent greater stimulation of NHE by Ang II in proximal tubules of obese rats. The greater stimulation of NHE by Ang II may contribute to the increased tubular sodium reabsorption and to the hypertension in obese Zucker rats.