Renal Angiotensin II Receptors,Hyperinsulinemia, and Obesity

Angiotensin II, via activation of AT₁ receptors in the kidney regulates sodium/fluid homeostasis and blood pressure. An exaggerated action of angiotensin II mediated via activation of AT₁ receptors has been implicated in the increased renal sodium retention and the resetting of the pressure natriuresis in obesity related hypertension. Treatment of obese Zucker rats with AT₁ receptor blockers reduces blood pressure to a greater extent and produces greater natriuresis. Also, there is an increased membranal AT₁ receptor numbers and angiotensin II produces greater activation of sodium transporters in the isolated tubules from obese Zucker rats. Interestingly, AT₂ receptors, which are believed to be beneficial to the renal and cardiovascular function in terms of their action on kidney and blood vessels, are greatly increased in proximal tubular membranes of obese Zucker rats. Whole animal and in vitro studies indicate that higher plasma insulin level, generally associated with obesity, is responsible for the up‐regulation of both AT₁ and AT₂ receptors in the kidney. Determining the consequence of selective blocking of AT₁ receptors and/or activation of the AT₂ receptors on renal and cardiovascular function, and the effect of lowering insulin on these receptors present an important area of further investigation in obesity.