Hyperinsulinemia and the aldosterone and pressor responses to angiotensin II.
To determine whether hyperinsulinemia alters angiotensin II-mediated aldosterone secretion, the increase in plasma aldosterone after intravenous angiotensin II (5, 10, and 20 ng/kg/min for 15 minutes each) was measured before and after euglycemic hyperinsulinemia in seven chronically instrumented dogs. In a random sequence on 4 successive days, dogs received either 0, 2, 4, or 8 milliunits/kg/min insulin. Euglycemic hyperinsulinemia, at all insulin doses, resulted in a significantly greater (p less than 0.01) change in the angiotensin II-stimulated increments of plasma aldosterone than was observed when angiotensin II was administered alone. However, there was no dose-dependence of insulin's effect on angiotensin II-stimulated aldosterone. The effect of weight gain on the angiotensin II response was also evaluated in five dogs. After weight gain, euglycemic hyperinsulinemia augmented angiotensin II-stimulated aldosterone to the same magnitude that was observed before weight gain. Possible mechanisms whereby insulin could increase angiotensin II-stimulated aldosterone production include: increased intracellular potassium, reduced plasma free fatty acids, and a direct action of insulin to induce increased adrenal steroidogenesis. In addition to altering the angiotensin II-aldosterone dose-response curve, hyperinsulinemia also increased the pressor action of angiotensin II. In contrast to the angiotensin II-aldosterone response, progressive hyperinsulinemia resulted in a progressive increase in the pressor response to angiotensin II. The increased pressor response is probably due to an increased activation of the sympathetic nervous system by insulin.
Section of Pediatric Cardiology, University of Michigan, Ann Arbor.
A P
AP
Rocchini
C
C
Moorehead
S
S
DeRemer
T L
TL
Goodfriend
D L
DL
Ball
D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007328:Insulin / Q000097:blood* / Q000494:pharmacology; D008297:Male; D009765:Obesity / Q000378:metabolism*; D012016:Reference Values
D007328:Insulin; D000804:Angiotensin II; D000450:Aldosterone