Role of the arterial baroreflex in the sympathetic response to hyperinsulinemia in adult humans

Am J Physiol Endocrinol Metab. 2022 Apr 1;322(4):E355-E365. doi: 10.1152/ajpendo.00391.2021. Epub 2022 Feb 21.

Abstract

Muscle sympathetic nerve activity (MSNA) increases during hyperinsulinemia, primarily attributed to central nervous system effects. Whether peripheral vasodilation induced by insulin further contributes to increased MSNA via arterial baroreflex-mediated mechanisms requires further investigation. Accordingly, we examined baroreflex modulation of the MSNA response to hyperinsulinemia. We hypothesized that rescuing peripheral resistance with coinfusion of the vasoconstrictor phenylephrine would attenuate the MSNA response to hyperinsulinemia. We further hypothesized that the insulin-mediated increase in MSNA would be recapitulated with another vasodilator (sodium nitroprusside, SNP). In 33 young healthy adults (28 M/5F), MSNA (microneurography) and arterial blood pressure (BP, Finometer/brachial catheter) were measured, and total peripheral resistance (TPR, ModelFlow) and baroreflex sensitivity were calculated at rest and during intravenous infusion of insulin (n = 20) or SNP (n = 13). A subset of participants receiving insulin (n = 7) was coinfused with phenylephrine. Insulin infusion decreased TPR (P = 0.01) and increased MSNA (P < 0.01), with no effect on arterial baroreflex sensitivity or BP (P > 0.05). Coinfusion with phenylephrine returned TPR and MSNA to baseline, with no effect on arterial baroreflex sensitivity (P > 0.05). Similar to insulin, SNP decreased TPR (P < 0.02) and increased MSNA (P < 0.01), with no effect on arterial baroreflex sensitivity (P > 0.12). Acute hyperinsulinemia shifts the baroreflex stimulus-response curve to higher MSNA without changing sensitivity, likely due to insulin's peripheral vasodilatory effects. Results show that peripheral vasodilation induced by insulin contributes to increased MSNA during hyperinsulinemia.NEW & NOTEWORTHY We hypothesized that elevation in muscle sympathetic nervous system activity (MSNA) during hyperinsulinemia is mediated by its peripheral vasodilator effect on the arterial baroreflex. Using three separate protocols in humans, we observed increases in both MSNA and cardiac output during hyperinsulinemia, which we attributed to the baroreflex response to peripheral vasodilation induced by insulin. Results show that peripheral vasodilation induced by insulin contributes to increased MSNA during hyperinsulinemia.

Keywords: autonomic nervous system; baroreflex sensitivity; blood pressure; insulin; peripheral resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Baroreflex*
  • Blood Pressure
  • Heart Rate
  • Humans
  • Hyperinsulinism*
  • Insulin / pharmacology
  • Muscle, Skeletal
  • Phenylephrine / pharmacology
  • Sympathetic Nervous System
  • Vasodilator Agents / pharmacology

Substances

  • Insulin
  • Vasodilator Agents
  • Phenylephrine