アンジオテンシンII AT₁受容体拮抗薬による高血圧自然発症ラットのインスリン感受性と交感神経機能への影響

抄録

Although angiotensin AT₁ receptor antagonist (A₁1 A) improves insulin sensitivity in insulin resistant models, its effect on spontaneously hypertensive rats (SHR) has not been elucidated. We investigated the effects of AT₁ A, candesartan on insulin sensitivity in SHR/Izm and the role of sympathetic activity in its mechanism. In 9-week-old SHR/Izm, candesartan (10 mg/kg/day) was given orally for 5 days. A control group received vehicle. On the 6th day, mean arterial pressure (MAP), heart rate (HR), plasma norepinephrine (PNE), plasma epinephrine (PE) and plasma dopamine (PDA) were measured in both groups (n = 11 in each group). In the separate groups of rats, fasting blood glucose (FBG), serum sodium, serum potassium and insulin sensitivity by steady state blood glucose (SSBG) were assessed (n=16 in the Candesartan group and n = 8 in the Control group). MAP and SSBG were significantly lower in the Candesartan group (117±2 mmHg and 138±5 mg/dl) than those in the Control group (155±6 mmHg and 164±10 mg/dl). Body weight, HR, FBG, PNE, PE, PDA, sodium and potassium were the same between the groups. In conclusion, since AT₁ A, candesartal lowers blood pressure and improves insulin sensitivity irrespective of sympathetic activity in SHR/Izm, it is useful in treating hypertension associated with insulin resistance.