ANGIOTENSIN RECEPTOR BLOCKADE BLUNTS HYPERINSULINEMIA-INDUCED HYPERTENSION IN RATS

The study was conducted to examine the effects of the angiotensin subt ype 1 and 2 receptor antagonists (losartan and PD123319, respectively) on blood pressure (BP) and renal excretory function in chronic hyperi nsulinemia-induced hypertension in rats. Hyperinsulinemia was achieved by insulin infusion (21.5 pmol/kg per minute) via osmotic minipump fo r 6 weeks. Losartan or PD123319 was coinfused either at the beginning or after 4 weeks of insulin infusion. The results showed that insulin infusion significantly increased the plasma insulin concentration from 259.0+/-22.2 to 646.5+/-33.0 and 713.9+/-26.5 pmol/L (P < 0.05) by th e end of the fourth and sixth weeks, respectively, after insulin infus ion. There were no significant changes in plasma glucose and triglycer ide concentrations. Systolic BP increased from 139+/-3 to 156+/-1 and 157+/-2 mm Hg (P < 0.05) at the corresponding time points. Combined lo sartan (3.5 mu g/kg per minute) and insulin infusion prevented the ris e in BP and improved insulin resistance. When hypertension had been es tablished after 4 weeks of insulin infusion, superimposed infusion of losartan on insulin reversed the elevated BP to control levels within 1 week. In contrast, administration of PD123319 (0.5 and 10 mu g/kg pe r minute) failed to alter insulin-induced hypertension. Combined PD123 319 with losartan did not alter the losartan-induced hypotensive effec t in insulin-infused rats. There were no significant differences in wa ter intake, urine flow, body weight gain, and sodium gain before and a fter antagonist administration among groups. These results indicate th at angiotensin type 1 receptors play a determinant role in the pathoge nesis of insulin-induced hypertension in rats.