Abstract 011: Chronic Renal-artery Infusion of Insulin+Glucose Increases Mean Arterial Pressure in Rats

Abstract

Obesity, metabolic syndrome, and Type 2 Diabetes are a continuum of hyperglycemia and hyperinsulinemia that is associated with hypertension. We have reported that inducing chronic hyperglycemia and hyperinsulinemia by continuous IV infusion increases blood pressure in rats. To test the hypothesis that a renal mechanism underlies the increase in blood pressure, we developed a method for chronic renal-artery (IR) infusion in rats. Male Sprague Dawley rats underwent right nephrectomy and a catheter was placed in the left renal artery. Artery and vein catheters and a DSI telemetry unit for 24 hr/day blood pressure also were implanted. Control IV and IR vehicle infusions were begun in all rats via dual-channel Instech swivels. Rats then were assigned randomly to receive either IV (n=11) insulin (1.5 mU/kg/min) and glucose (20 mg/kg/min) or IR (n=8) insulin and glucose at 20% of the IV doses. The alternate syringe in each group continued with the control vehicle solution. MAP averaged 108±1 and 110±2 mmHg in IV and IR rats, respectively, during control, increased progressively and significantly in both groups during 7 days of insulin+glucose infusion, and returned towards control during recovery. Cumulative sodium balance increased significantly in both groups, with no significant change in GFR in either group. Blood glucose did not change significantly and did not differ between groups. Plasma insulin (uU/ml) did not change significantly in the IR rats (8.3±2.6 to 4.8±1.2), but increased significantly in the IV group (13.3±5.5 to 27.9±4.9). These data suggest that chronic hyperinsulinemia and hyperglycemia increase arterial pressure through a direct action on the kidneys.