Chronic adrenergic receptor blockade does not prevent hyperinsulinemia-induced hypertension in rats

Increased adrenergic activity has been suggested to mediate the hypertension associated with hyperinsulinemia. This study tested whether combined alpha1- and beta-adrenergic receptor blockade would prevent insulin-induced hypertension when euglycemia was maintained by continuous intravenous glucose infusion. Sprague-Dawley rats (n = 16) were instrumented with artery and vein catheters and placed in metabolic cages. Propranolol and prazosin (10 mg/kg/day each) were infused continuously intravenously in 9 rats and 7 other rats received vehicle. Mean arterial pressure (MAP) and heart rate (HR) were measured 24 h per day using computerized methods. After a control period, a 7-day intravenous infusion of insulin (1.5 microU/kg/min) was begun and glucose was coadministered intravenously at 23 mg/kg/min to prevent hypoglycemia. The MAP averaged 93 +/- 1 mm Hg in the blockade rats during the control period, which was significantly lower than the 98 +/- 1 mm Hg in the normal rats. During insulin infusion, MAP increased similarly in both groups, with a 10 +/- 2 mm Hg and 11 +/- 1 mm Hg increase in normal and blockade rats, respectively, by day 7. The HR also increased in both groups: from 417 +/- 8 beats/ min to 426 +/- 13 beats/min (P = NS) in normal rats and from 379 +/- 10 beats/min to 419 +/- 10 beats/min (P < .05) in blockade rats. Control sodium excretion averaged 2.5 +/- 0.1 mEq/day in both groups and no significant change in sodium balance was measured in either group. All variables returned toward control after stopping insulin. These results suggest that increased adrenergic activity is not required for chronic hyperinsulinemia to raise blood pressure in rats.