Ghrelin potentiates cardiac reactivity to stress by modulating sympathetic control and beta-adrenergic response

Life Sci. 2018 Mar 1:196:84-92. doi: 10.1016/j.lfs.2018.01.019. Epub 2018 Feb 3.

Abstract

Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress.

Aims: In the present study, we assessed the role of ghrelin - GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats.

Main methods and key findings: Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the perfusion with ghrelin potentiated the contractile responses caused by stimulation of the beta-adrenergic receptor, without altering the amplitude of the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes revealed that ghrelin amplified the increases in calcium transient changes evoked by isoproterenol.

Significance: Taken together, our results indicate that the Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by modulating the autonomic nervous system and peripheral mechanisms, strongly relying on the activation of cardiac calcium transient and beta-adrenergic receptors.

Keywords: Beta-adrenergic receptors; Cardiac calcium transient; Emotional stress; GHS-R1a receptor; Ghrelin; Heart rate.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Arterial Pressure / drug effects
  • Calcium Channels / drug effects
  • Ghrelin / pharmacology*
  • Heart / drug effects*
  • Heart / innervation
  • Heart Rate / drug effects
  • In Vitro Techniques
  • Male
  • Muscarinic Agonists / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta / drug effects*
  • Receptors, Ghrelin / drug effects
  • Restraint, Physical
  • Stress, Psychological / physiopathology*
  • Sympathetic Nervous System / drug effects*
  • Tachycardia / chemically induced
  • Tachycardia / physiopathology

Substances

  • Adrenergic beta-Agonists
  • Calcium Channels
  • Ghrelin
  • Muscarinic Agonists
  • Receptors, Adrenergic, beta
  • Receptors, Ghrelin