Role of angiotensin II in hyperinsulinemia-induced hypertension in rats.
OBJECTIVE: To investigate the role of angiotensin II in the pathogenesis of hyperinsulinemia-induced hypertension in rats. MATERIALS AND METHODS: Chronic hyperinsulinemia was achieved by infusing insulin (3 mU/kg per min) subcutaneously by an osmotic minipump for 6 weeks. An angiotensin converting enzyme inhibitor (fosinopril, 10 mg/kg per day) was added in drinking water and the angiotensin II subtype 1 receptor antagonist losartan (3.5 microg/kg per min) was co-infused via the minipump. Control rats were administered the vehicle only. The rats were housed in individual metabolic cages and fed a sodium-controlled diet. Food and water intake and urine output were measured daily. Systolic blood pressure and heart rate were measured by the tail-cuff method twice a week. RESULTS: By the end of weeks 4 and 6 of the sustained insulin infusion, systolic blood pressure had increased significantly (P < 0.05), from 134+/-1 to 157+/-2 and 158+/-2 mmHg, respectively, and the heart rate had increased significantly (P< 0.05), from 380+/-9 to 423+/-7 and 426+/-6 beats/min, respectively. The plasma insulin concentration increased by 2-2.5 times but no significant changes in plasma glucose and triglyceride levels were noted. Concomitant treatment with fosinopril prevented the rises in systolic blood pressure and heart rate in the insulin-infused rats. When the insulin-induced hypertension had become established (systolic blood pressure increased from 132+/-3 to 155+/-2 mmHg 4 weeks after the infusion, P< 0.05 ), subsequent fosinopril or losartan treatment for 2 weeks reversed the elevated systolic blood pressure and heart rate to the control levels. There were no significant differences in water intake, urine flow, sodium gain and body weight gain between the control and the insulin-infused rats. CONCLUSIONS: Angiotensin converting enzyme inhibition or angiotensin II type 1 receptor antagonism can prevent and reverse insulin-induced hypertension in rats, suggesting that angiotensin II itself or an angiotensin II-dependent mechanism has an etiological influence in the pathogenesis of this hypertension model.[1]References
- Role of angiotensin II in hyperinsulinemia-induced hypertension in rats. Fang, T.C., Huang, W.C. J. Hypertens. (1998) [Pubmed]
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