AT2 receptor protects high sodium‐induced decrease in ACE2/Mas receptor expression and increase in blood pressure in obese rats (1136.8)

Abstract

High sodium (Na) intake is a risk factor for the pathogenesis of hypertension, especially in obesity. Whereas high Na diet increases blood pressure (BP) associated with a decrease in renal MasR/ACE2 expression, chronic AT2R stimulation lowers BP concomitant with an increase in MasR/ACE2 expression in obese Zucker rats. However, role of AT2R in high Na‐induced hypertension and regulation of ACE2/MasR expression in obesity is not known. Male obese rats were treated with AT2R agonist C21 (1mg/kg/day oral) while maintained on either normal (NSD, 0.4%) or high Na diet (HSD, 4%) for 2‐weeks. Telemetry monitoring of BP showed an increase in systolic BP (SBP) by 20 mm Hg in obese HSD compared to NSD group; which was prevented by C21 treatment. Compared to control, HSD caused diuresis which was further increased in HSD+C21 group. The rats on HSD had increase in body and kidney weight; which was lowered by C21 treatment. HSD reduced the cortical MasR and ACE2 activity which was increased by C21 treatment. AT2R, ACE expression and renin activity were same in all the groups. However AT1R, although unchanged with HSD or C21 treatment, was decreased in HSD+C21 group. This study clearly demonstrate that chronic AT2R agonist treatment prevents high Na‐induced increase in BP which was associated with an increase in the beneficial ACE2/MasR axis in obese rats indicating the potential role of AT2R against Na‐sensitive hypertension in obesity.Grant Funding Source: NIH R01‐DK61578