Endogenous adenosine release is involved in the control of heart rate in rats

Can J Physiol Pharmacol. 2015 Aug;93(8):667-75. doi: 10.1139/cjpp-2015-0042. Epub 2015 Apr 1.

Abstract

Intravenous (i.v.) injections of adenosine exert marked effects on heart rate (HR) and arterial blood pressure (BP), but the role of an endogenous adenosine release by vagal stimulation has not been evaluated. In anaesthetized rats, we examined HR and BP changes induced by 1 min electrical vagal stimulation in the control condition, and then after i.v. injections of (i) atropine, (ii) propranolol, (iii) caffeine, (iv) 8 cyclopentyl-1,3-dipropylxanthine (DPCPX), or (v) dipyridamole to increase the plasma concentration of adenosine (APC). APC was measured by chromatography in the arterial blood before and at the end of vagal stimulation. The decrease in HR in the controls during vagal stimulation was markedly attenuated, but persisted after i.v. injections of atropine and propranolol. When first administered, DPCPX modestly but significantly reduced the HR response to vagal stimulation, but this disappeared after i.v. caffeine administration. Both the HR and BP responses were significantly accentuated after i.v. injection of dipyridamole. Vagal stimulation induced a significant increase in APC, proportional to the magnitude of HR decrease. Our data suggest that the inhibitory effects of electrical vagal stimulations on HR and BP were partly mediated through the activation of A1 and A2 receptors by an endogenous adenosine release. Our experimental data could help to understand the effects of ischemic preconditioning, which are partially mediated by adenosine.

Keywords: adenosine; blood pressure; fréquence cardiaque; heart rate; innervation sympathique; nerf vague; pression artérielle; rat; sympathetic innervation; vagus nerve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / blood
  • Adenosine / metabolism*
  • Adrenergic beta-Antagonists / administration & dosage
  • Animals
  • Blood Pressure / drug effects
  • Heart / innervation*
  • Heart Rate* / drug effects
  • Injections, Intravenous
  • Muscarinic Antagonists / administration & dosage
  • Purinergic P1 Receptor Antagonists / administration & dosage
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P1 / drug effects
  • Receptors, Purinergic P1 / metabolism
  • Signal Transduction / drug effects
  • Vagus Nerve / physiology*
  • Vagus Nerve Stimulation

Substances

  • Adrenergic beta-Antagonists
  • Muscarinic Antagonists
  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1
  • Adenosine