Chronic exercise improves renal AT1 and ETB receptor functions via modulating GRK4 expression in obese Zucker rats.

Background: Physical activity has profound benefits on health, especially in patients with cardiovascular and metabolic disease. Exercise training can reduce oxidative stress, improve renal function, and thus lower blood pressure. However, the effect of exercise training on angiotensin II type 1 receptors (AT₁R) and endothelin subtype B receptors (ETBR)-mediated diuresis and natriuresis in obese Zucker rats is unclear.

Methods: Lean and obese Zucker rats were exercised or placed on a nonmoving treadmill for 8 weeks. Blood pressure was measured by tail-cuff plethysmography, and functions of AT₁R and ETBR in the kidney were measured by natriuresis, respectively.

Results: Our data showed that exercise training improved glucose and lipid metabolism, renal function and sodium excretion in obese Zucker rats, accompanied by decreased oxidative stress and GRK4 expression in obese Zucker rats. Moreover, exercise training reduced the Candesartan-induced an increase in diuresis and natriuresis and increased ETBR agonists (BQ3020)-mediated diuresis and natriuresis in obese Zucker rats, which were associated with decreased renal AT₁R expression and ETBR phosphorylation levels.

Conclusions: The results demonstrate that exercise training lowers blood pressure via improving renal AT₁R and ETBR function through modulating GRK4 expression in Obese Zucker Rats and provides potentially effective targets for obesity-related hypertension.