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 suggestedas a pathogenetic mechanism in hypertension. METHODS: In this investigation the renal response to insulin was studiedin normotensive subjects with a positive family history of hypertensionin two generations (n = 14), in one weight-matched (n = 11)and one lean (n = 13) control group. During hyperinsulinaemia(euglycaemic hyperinsulinaemic clamp technique) we determinedrenal haemodynamics (clearances of ⁵¹Cr-EDTA and PAH) and urinarysodium excretion. Lithium clearance was used to estimate thesegmental tubular reabsorption of sodium. RESULTS: In subjects with a positive family history of hypertension,hyperinsulinaemia did not influence renal plasma flow (RPF)or glomerular filtration rate (GFR) but urinary sodium excretiondecreased by 50%. Estimated proximal tubular sodium reabsorptionwas unaffected by insulin while estimated distal fractionalsodium reabsorption increased, P<0.01. At the end of theclamp a low-dose infusion of angiotensin II (0.1 ng/kg per min)was superimposed. GFR and RPF then decreased significantly concomitantwith urinary excretion of sodium. In control subjects hyperinsulinaemia caused an unchanged GFRin both groups, increased RPF in the lean control group and15–25% reduction in sodium excretion. No alteration wasseen in estimated proximal tubular sodium reabsorption, butestimated distal tubular sodium reabsorption increased (P<0.05)in the lean control group. Angiotensin II elicited a furtherincrease in distal fractional tubular sodium reabsorption inboth control groups (P<0.05). CONCLUSIONS: In normotensive subjects with a positive family history of hypertension,in contrast to control subjects without such history, hyperinsulinaemiacaused a marked decrease in urinary sodium excretion in presenceof unchanged RPF and GFR indicating a renal tubular effect ofinsulin located at a distal site of the renal tubules. AngiotensinII caused further sodium retention, probably due to an effecton renal haemodynamics.