RENAL AND CARDIOVASCULAR EFFECTS OF EXOGENOUS INSULIN IN HEALTHY-VOLUNTEERS

1. Renal and cardiovascular effects of three dosages of insulin [50 (Ins I), 300 (Ins II) and 500 (Ins III) m-units h-1 kg-1] were investigated in healthy males by using a euglycaemic clamp technique. On separate days, control experiments were carried out to correct for any circadian variation in the variables studied. 2. All three insulin dosages resulted in a marked decline in fractional sodium excretion (actual experiments: basal, 0.95 +/- 0.15%, Ins I, 0.79 +/- 0.10%, Ins II, 0.80 +/- 0.12%, Ins III, 0.84 +/- 0.08%; control experiments: basal, 0.96 +/- 0.10%, Ins I, 1.20 +/- 0.12%, Ins II, 1.53 +/- 0.15%, Ins III, 1.43 +/- 0.10%; means +/- SEM, P < 0.005, analysis of variance). With the highest insulin dosage, the reduction in fractional sodium excretion tended to be less striking. This coincided with a rise in heart rate, pulse pressure and pulse rate-systolic blood pressure product (double product). Although blood pressure itself did not change, systolic blood pressure also tended to increase (actual experiments: basal, 133 +/- 5 mmHg, Ins I, 132 +/- 5 mmHg, Ins II, 139 +/- 5 mmHg, Ins III, 143 +/- 4 mmHg; control experiments: basal, 128 +/- 3 mmHg, Ins I, 129 +/- 3 mmHg, Ins II, 130 +/- 3 mmHg, Ins III, 133 +/- 3 mmHg; means +/- SEM, P = 0.09, analysis of variance). There was a positive correlation between the change in fractional sodium excretion and the change in systolic blood pressure over control values (r = 0.696, P < 0.028). At a rise systolic blood pressure of 18 mmHg, the sodium-retaining effect of insulin appeared to be offset. A shift of the pressure-natriuresis relation to the right is suggested. 3. Plasma catecholamines did not change. Plasma renin activity increased from 1.11 +/- 0.17 (basal) to 2.13 +/- 0.31 (Ins III) pmol of angiotensin I h-1 ml-1; on the control day, a decline from 1.28 +/- 0.24 (basal) to 0.81 +/- 0.13 (Ins III) pmol of angiotensin I h-1 ml-1 was noted (P < 0.001). Despite this rise no concomitant rise in plasma aldosterone occurred. 4. Chronic hyperinsulinaemia may lead to blood pressure elevation in the long-term if it is postulated that resistance to the glucose-lowering effect of insulin is absent for the effects of insulin on the kidney and the cardiovascular system.