STIMULATORY EFFECT OF INSULIN ON TUBULAR SODIUM-REABSORPTION IN NORMOTENSIVE SUBJECTS WITH A POSITIVE FAMILY HISTORY OF HYPERTENSION

Background. Insulin resistance and hyperinsulinaemia has been suggeste d as a pathogenetic mechanism in hypertension. Methods. In this invest igation the renal response to insulin was studied in normotensive subj ects with a positive family history of hypertension in two generations (n = 14), in one weight-matched (n = 11) and one lean (n = 13) contro l group. During hyperinsulinaemia (euglycaemic hyperinsulinaemic clamp technique) we determined renal haemodynamics (clearances of Cr-51-EDT A and PAH) and urinary sodium excretion. Lithium clearance was used to estimate the segmental tubular reabsorption of sodium. Results. In su bjects with a positive family history of hypertension, hyperinsulinaem ia did not influence renal plasma flow (RPF) or glomerular filtration rate (GFR) but urinary sodium excretion decreased by 50% Estimated pro ximal tubular sodium reabsorption was unaffected by insulin while esti mated distal fractional sodium reabsorption increased, P<0.01. At the end of the clamp a low-dose infusion of angiotensin II (0.1 ng/kg per min) was superimposed. GFR and RPF then decreased significantly concom itant with urinary excretion of sodium. In control subjects hyperinsul inaemia caused an unchanged GFR in both groups, increased RPF in the l ean control group and 15-25% reduction in sodium excretion. No alterat ion was seen in estimated proximal tubular sodium reabsorption, but es timated distal tubular sodium reabsorption increased (P<0.05) in the l ean control group. Angiotensin II elicited a further increase in dista l fractional tubular sodium reabsorption in both control groups (P<0.0 5). Conclusions. In normotensive subjects with a positive family histo ry of hypertension, in contrast to control subjects without such histo ry, hyperinsulinaemia caused a marked decrease in urinary sodium excre tion in presence of unchanged RPF and GFR indicating a renal tubular e ffect of insulin located at a distal site of the renal tubules. Angiot ensin II caused further sodium retention, probably due to an effect on renal haemodynamics.