The effect of apelin-13 on gastric ischemia/reperfusion injury: the roles of sensory nerves and vagus nerve

Can J Physiol Pharmacol. 2020 May;98(5):282-295. doi: 10.1139/cjpp-2019-0502. Epub 2019 Dec 10.

Abstract

Apelin is a peptide that plays a role in physiological processes such as angiogenesis, apoptosis, and proliferation. The aim of this study was to investigate the role of capsaicin-sensitive afferent neurons and vagus in the effect of apelin against ischemia/reperfusion (I/R) injury. The experimental groups were (1) control, (2) I/R, (3) apelin + I/R, (4) vagotomy + I/R, (5) vagotomy + apelin + I/R, (6) capsaicin + I/R, (7) capsaicin + apelin + I/R, (8) lorglumide + I/R, and (9) lorglumide + apelin + I/R. To test the potential gastroprotective effect of apelin-13, apelin-13 (2 mg/kg i.v.) was administered just before both ischemia and reperfusion. A vagotomy was performed 1 week before I/R in the vagotomized groups; capsaicin (125 mg/kg s.c.) was administrated 2 weeks before I/R in the capsaicin-treated groups and lorglumide (5 mg/kg i.p.) was administered 30 min before I/R in the lorglumide-treated groups. After I/R, a variety parameters in gastric tissue were analyzed. cfos expression was determined in brainstem samples. In the I/R group, the lesion index, myeloperoxidase activity, lipid peroxidation, nitric oxide, and tumor necrosis factor-α increased, and mucosal blood flow, prostaglandin-E2, and calcitonin gene related peptide decreased. Apelin prevented the damaging effects of I/R and increased cfos expression in brainstem areas. Vagotomy, capsaicin, and lorglumide largely eliminated the gastroprotective effects of apelin-13. This study showed that sensory nerves and the vagus play regulatory roles in apelin-induced gastroprotection. Cholecystokinin may play a role in the effect of apelin through sensory neurons.

Keywords: apelin; apeline; dorsal motor nucleus of vagus; ischemia/reperfusion; ischémie/reperfusion; nerfs sensoriels; noyau moteur dorsal du nerf vague; sensory nerves; vague; vagus.

MeSH terms

  • Animals
  • Cytoprotection / drug effects
  • Dinoprostone / metabolism
  • Dose-Response Relationship, Drug
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Male
  • Nitric Oxide / metabolism
  • Peroxidase / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Cholecystokinin B / metabolism
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology*
  • Sensory Receptor Cells / drug effects*
  • Sensory Receptor Cells / pathology
  • Stomach / drug effects*
  • Stomach / innervation*
  • Vagus Nerve / drug effects*
  • Vagus Nerve / physiopathology

Substances

  • Intercellular Signaling Peptides and Proteins
  • Receptor, Cholecystokinin B
  • apelin-13 peptide
  • Nitric Oxide
  • Peroxidase
  • Dinoprostone