THE EFFECT OF ANGIOTENSIN-I CONVERTING ENZYME-INHIBITION ON INSULIN ACTION IN HEALTHY-VOLUNTEERS

Acute hyperinsulinaemia, achieving insulin levels within the physiological range, induces sodium retention. At the same time an activation of the renin-angiotensin system occurs, with a rise in plasma renin activity (PRA) and angiotensin-II level but no change in plasma aldosterone. After administration of higher, pharmacological doses of insulin an increase in systolic blood pressure and heart rate can also be observed, while further increases in PRA and angiotensin-II are noted. To determine whether angiotensin-II is involved in observed insulin actions, we studied the renal and cardiovascular effects of three dosages of insulin (50 (Ins I), 300 (Ins II) and 500 (Ins III) mU kg-1 h-1) in healthy subjects after one week of treatment with the angiotensin-I converting enzyme inhibitor enalapril (10 mg twice a day), using the euglycaemic clamp technique. Control data were obtained from two previously conducted experiments in the same subjects, one with infusion of insulin and one with the insulin solvent only. The effect of insulin on fractional sodium excretion, blood pressure and heart rate was unaffected by enalapril, which precludes any involvement of the renin-angiotensin system with regard to these aspects of insulin action. Insulin sensitivity increased significantly during treatment with enalapril (with enalapril: Ins I: 11.3 +/- 3.0, Ins II: 20.0 +/- 3.4 and Ins III: 20.6 +/- 3.9 mg kg-1 min-1 glucose (mean +/- SD); without enalapril: Ins I: 8.7 +/- 2.3, Ins II: 13.7 +/- 3.0 and Ins III: 15.5 +/- 3.1 mg kg-1 min-1 glucose; P < 0.05). When this latter finding can be confirmed in a randominized study, enhancement of tissue sensitivity to the glucose-lowering actions of insulin by enalapril must be considered a property common to all members of this class of drugs.