EFFECTS OF INSULIN ON RENAL-FUNCTION, SYMPATHETIC NERVOUS ACTIVITY AND FOREARM BLOOD-FLOW IN NORMAL HUMAN-SUBJECTS

Objective: To assess fully the vasodilatory and sodium-retaining effec ts of insulin. Design: Prospective physiologic study using a dose-resp onse protocol. Setting: Clinical investigation unit of a tertiary refe rral hospital. Participants: Six normal, healthy men. Interventions: S ubjects were given increasing doses of insulin intravenously from 10 t o 1200 mU/m(2) per minute, using the euglycemic ''clamp'' technique. O utcome measures: Urinary sodium excretion, systemic and renal hemodyna mics, plasma norepinephrine levels and forearm blood flow after each d ose. Results: Low doses of insulin (up to 20 mU/m(2) per minute) produ ced a significant antinatriuresis (0.18 [SEM 0.05] v. 0.37 mmol per mi nute at baseline, p < 0.01) and antidiuresis (2.53 [SEM 0.67] v. 6.21 [SEM 1.66] mt per minute, p < 0.01) with no associated changes in rena l hemodynamics or sympathetic nervous activity. Subsequent higher dose s of insulin improved urinary volume and sodium excretion to above bas eline levels associated with renal and forearm vasodilatation, althoug h mean arterial pressure remained unaltered. Conclusions: Hyperinsulin emia initially causes an antinatriuresis and antidiuresis through a di rect action on the renal tubule. The subsequent phenomenon of escape f rom renal sodium retention may serve as a regulatory mechanism on sodi um homeostasis in conditions associated with hyperinsulinemia and sodi um retention.