Abstract 013: Chronic Intra-Renal Insulin Infusion Increases Mean Arterial Pressure on a Background of Mild Angiotensin II Hypertension

Abstract

We reported that chronic intra-renal insulin infusion in diabetic dogs reversed the natriuresis and diuresis caused by 6 days of hyperglycemia. However, the sustained sodium-retaining action was not accompanied by hypertension. This study tested whether intra-renal insulin infusion would increase blood pressure in diabetic dogs with chronic angiotensin II (AngII) hypertension. Seven dogs were chronically instrumented and divided into D (diabetes) and Dir (D + intra-renal insulin) groups. Alloxan was administered to all 7 dogs, and continuous iv. insulin replacement therapy was used to maintain them at normal blood glucose. All dogs also were infused with AngII (3 ng/kg/min, iv) continuously. After 3 days of control measurements, with normal blood glucose, MAP averaged 135±3 and 129±3 mmHg in D and Dir dogs, respectively. Six days of hyperglycemia (diabetes) was induced in both groups by reducing the iv. insulin infusion dose. Intra-renal insulin at 0.3 mU/kg/min was initiated concurrently in the Dir dogs. MAP increased in the Dir group to an average of 141±4 mmHg by day 6 of diabetes. Moreover, Figure 1 shows the progressive separation in MAP compared to the D dogs, to an average difference of 19 mmHg by day 6 of diabetes. Renal blood flow (measured 24 hr/day along with MAP) increased in both groups, as did GFR. However, statistically significant differences were not achieved yet with these preliminary data. These results suggest that the chronic antinatriuretic effect of insulin in diabetes may have an AngII-dependent hypertensive action. The mechanism does not appear to be dependent on renal vasoconstriction, and may, therefore, be linked to effects on tubular sodium reabsorption.