Chronic intrarenal hyperinsulinemia in hyperglycemic dogs causes sodium retention and increases mean arterial pressure

We recently showed that the sustained natriuresis in dogs with Type I diabetes is due to the decrease in insulin rather than the hyperglycemia alone. The sodium retaining action of insulin appeared to require hyperglycemia; however, it served to prevent sodium loss rather than increase sodium balance, and there was no increase in mean arterial pressure (MAP). This study tested whether intrarenal hyperinsulinemia would cause sodium retention and increased blood pressure under less severe hyperglycemic conditions. Alloxan‐treated dogs (n=3) were maintained normoglycemic using 24 hr/day iv. insulin replacement. After control measurements, iv. insulin was stopped and replaced with chronic intrarenal insulin infusion at 0.6 mU/kg/min for 6 days, and followed by a recovery period. Blood glucose increased from 113 to 141 mg/dl, and plasma insulin increased from 2.5 to 4.4 uU/ml, over the 6‐day period. Sodium excretion (UNaV) decreased from 78±8 to 54±12 mEq/d on day 1 and averaged 48±10 mEq/d for the 6‐days. GFR and RBF increased. Cumulative balance increased by 168±18 mEq, and UNaV surged to ~ 120 mEq/d for the first 2 days after stopping intrarenal insulin. MAP increased progressively from 102±4 to 110±5 mmHg by day 6, and was back to 102±3 mmHg by day 5 of recovery. Thus, insulin significantly increased renal sodium reabsorption under hyperglycemic conditions, and this action may underlie the increase in MAP. (HL56259)