Intranasal oxytocin has sympathoexcitatory effects on vascular tone in healthy males

Am J Physiol Regul Integr Comp Physiol. 2021 Feb 1;320(2):R162-R172. doi: 10.1152/ajpregu.00062.2020. Epub 2020 Dec 9.

Abstract

Oxytocin appears to be involved in the neuroendocrine regulation of sympathetic blood pressure (BP) homeostasis. In animals, intracerebral administration of oxytocin induces BP-relevant sympathetic activation. In humans, central nervous effects of oxytocin on BP regulation remain unclear. Intranasal administration supposedly delivers oligopeptides such as oxytocin directly to the brain. We investigated the effects of intranasal oxytocin on sympathetic vascular baroreflex function in humans using microneurographic techniques. In a balanced, double-blind crossover design, oxytocin or placebo was administered intranasally to 12 lean, healthy males (age 25 ± 4 yr). Muscle sympathetic nerve activity (MSNA) was assessed microneurographically before (presubstance), 30-45 min (postsubstance I), and 105-120 min (postsubstance II) after oxytocin administration. Baroreflex was challenged via graded infusions of vasoactive drugs, and correlation of BP with MSNA and heart rate (HR) defined baroreflex function. Experiments were conducted in the afternoon after a 5-h fasting period. After oxytocin, resting MSNA (burst rate and total activity) showed significant net increases from pre to postsubstance II compared with placebo [Δincrease = +4.3 ± 1.2 (oxytocin) vs. +2.2 ± 1.4 bursts/min (placebo), ANOVA; P < 0.05; total activity = 184 ± 11.5% (oxytocin) vs. 121 ± 14.3% (placebo), ANOVA; P = 0.01). This was combined with a small but significant net increase in resting diastolic BP, whereas systolic and mean arterial BP or HR as well as baroreflex sensitivity at vasoactive drug challenge were not altered. Intranasally administered oxytocin induced vasoconstrictory sympathoactivation in healthy male humans. The concomitant increase of diastolic BP was most likely attributable to increased vascular tone. This suggests oxytocin-mediated upward resetting of the vascular baroreflex set point at centers superordinate to the mere baroreflex-feedback loop.

Keywords: autonomic nervous system; baroreflex; intranasal oxytocin; muscle sympathetic nerve activity (MSNA); sympathetic nervous system.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Adult
  • Cross-Over Studies
  • Double-Blind Method
  • Humans
  • Male
  • Nitroglycerin / administration & dosage
  • Nitroglycerin / pharmacology
  • Oxytocics / administration & dosage*
  • Oxytocics / pharmacology*
  • Oxytocin / administration & dosage*
  • Oxytocin / pharmacology*
  • Phenylephrine / administration & dosage
  • Phenylephrine / pharmacology
  • Sympathomimetics / administration & dosage
  • Sympathomimetics / pharmacology
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / pharmacology
  • Young Adult

Substances

  • Oxytocics
  • Sympathomimetics
  • Vasodilator Agents
  • Phenylephrine
  • Oxytocin
  • Nitroglycerin