EFFECTS OF THE GLUCOCORTICOID-II RECEPTOR ANTAGONIST MIFEPRISTONE ON HYPERTENSION IN THE OBESE ZUCKER RAT

We have investigated the possible involvement of endogenous corticoste roids in the maintenance of hypertension in aged lean and obese Zucker rats using the type II corticosteroid antagonist mifepristone. At 8 m o of age, the start of the study, obese Zuckers had been hypertensive for at least 2 mo (systolic blood pressure; 153 +/- 4 vs. 136 +/- 5 mm Hg; n = 8-9; P < .05) and were hyperinsulinemic (756 +/- 98 vs. 193 +/ - 61 mu U . ml(-1)) and hypercorticosteronemic (524 +/- 83 vs. 260 +/- 97 ng . ml(-1)) compared to their lean littermates. There were no dif ferences in plasma renin activity between lean and obese animals and p lasma renin activity was unaffected by any treatment. Oral treatment o f obese rats with mifepristone (40.0 mg.kg(-1) day(-1) for 9 days) res ulted in a gradual reduction in SBP to lean levels by day 9. Mifeprist one treatment did not affect plasma insulin or corticosterone levels b ut resulted in a significant reduction in plasma aldosterone concentra tion. Mifepristone was without significant effect on systolic blood pr essure in lean rats. Oral treatment of lean rats with corticosterone-2 1-acetate (3.0 mg . kg(-1) day(-1) for 9 days) resulted in a rise in s ystolic blood pressure to levels similar to obese Zuckers after 9 days . Plasma insulin levels were unchanged but corticosterone immunoreacti vity was significantly reduced. Plasma aldosterone levels were increas ed from 564 +/- 3 to 802 +/- 68 pg . ml(-1). Our data suggest that rai sed glucocorticoids and aldosterone may be factors contributing to hyp ertension in obesity.