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 relationship between the sodium-retaining actions of insulin and atrial natriuretic factor (ANF), 16 healthy subjects were studied on three occasions, approximately 1 wk apart, using standard clearance techniques to evaluate responses during the acute administration of insulin, low-dose ANF, or both. In study 1, the euglycemic clamp was used to increase 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) independent of change in renal hemodynamics, lithium clearance, and catecholamines. The decline in sodium excretion was associated with a marked increase in fractional distal sodium reabsorption. Systolic and diastolic pressure did not change significantly. In study 2, low-dose ANF (0.3 pmol.kg-1.min-1) designed to raise plasma levels to twice baseline was administered simultaneously in a repeat of study 1. This maneuver abolished insulin-mediated sodium reabsorption. In study 3, low-dose ANF infusion alone produced no changes in tubular handling of sodium. Our findings indicate that insulin at levels found in hyperinsulinemic states caused sodium retention and that physiological increases in plasma ANF concentration abolished the sodium-retaining action of insulin. Our findings suggest that if hypertension is causally related to hyperinsulinemia, mechanisms besides renal sodium retention are responsible for the hypertensive properties of insulin.
Miller
J A
JA
Department of Medicine, University of Toronto, Ontario, Canada.
Abouchacra
S
S
Zinman
B
B
Skorecki
K L
KL
Logan
A G
AG
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology*; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D015309:Glucose Clamp Technique; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*
D007328:Insulin; D009320:Atrial Natriuretic Factor; D012964:Sodium; D006152:Cyclic GMP