ATRIAL-NATRIURETIC-FACTOR COUNTERACTS SODIUM-RETAINING ACTIONS OF INSULIN IN NORMAL MEN

It has been hypothesized that hyperinsulinemia is causally related to hypertension by its effect on renal sodium transport. To examine the r elationship between the sodium-retaining actions of insulin and atrial natriuretic factor (ANF), 16 healthy subjects were studied on three o ccasions, approximately 1 wk apart, using standard clearance technique s to evaluate responses during the acute administration of insulin, lo w-dose ANF, or both. In study 1, the euglycemic clamp was used to incr ease plasma insulin 10-fold to an average of 320 +/- 14 (SE) pM. This maneuver produced an immediate and persistent fall in sodium excretion from 0.315 +/- 0.02 to 0.207 +/- 0.02 mmol/min (P < 0.001) independen t of change in renal hemodynamics, lithium clearance, and catecholamin es. The decline in sodium excretion was associated with a marked incre ase in fractional distal sodium reabsorption. Systolic and diastolic p ressure did not change significantly. In study 2, low-dose ANF (0.3 pm ol.kg-1.min-1) designed to raise plasma levels to twice baseline was a dministered simultaneously in a repeat of study 1. This maneuver aboli shed insulin-mediated sodium reabsorption. In study 3, low-dose ANF in fusion alone produced no changes in tubular handling of sodium. Our fi ndings indicate that insulin at levels found in hyperinsulinemic state s caused sodium retention and that physiological increases in plasma A NF concentration abolished the sodium-retaining action of insulin. Our findings suggest that if hypertension is causally related to hyperins ulinemia, mechanisms besides renal sodium retention are responsible fo r the hypertensive properties of insulin.