The role of capsaicin sensitive sensory nerves and N. vagus in the protective effect of apelin against to ischemia/reperfusion injury

Objective: Apelin is a peptide produced in many tissues and found to play a role in physiological events such as angiogenesis, apoptosis and proliferation. The aim of this study is to investigate the role of capsaicin sensitive afferent nerves and n. vagus in the protective effect of apelin against ischemia/reperfusion (I/R) mediated gastric injury. Method: The study with 108 Wistar male rats consisted of, 1) Control; 2) I/R; 3) Vagotomy+I/R; 4) Capsaicin+I/R; 5) Lorglumide+I/R; 6) Apelin+I/R; 7) Vagotomy+Apelin+I/R; 8) Capsaicin+Apelin+I/R and 9) Lorglumide+Apelin+I/R groups. I/R injury in the gastric mucosa was induced by clamping celiac artery for 30 min and followed by to obtain reperfusion for 3 hours. While in the apelin-treated groups, apelin-13 (2 mg/kg, i.v.) was administered immediately before I/R, in the vagotomy-treated groups, vagotomy was performed 1 week before I/R; in the capsaicin-treated groups, capsaicin (125 mg/kg, s.c.) was administrated 2 weeks before and in the lorglumide-treated group, lorglumide (5 mg/kg, i.p.) was administered 30 min before I/R. After the I/R, GMBF was measured and area of mucosal lesions were determined. Gastric specimens were used to measure for mucus, MPO activity, LPO, TNF-α, PGE2, NO and CGRP; brainstem samples were used for cfos expression in DMN and NTS. Results: In the I/R group, lesion index, MPO activity, LPO, NO, TNF-α and mucus increased; mucosal blood flow, PGE2 and CGRP were significantly decreased. Pretreatment with apelin prevented the effects of I/R injury and increased cfos expression in DMN and NTS. Vagotomy, capsaicin and lorglumide have largely eliminated the protective effect of apelin against I/R injury and has been shown to have a role of CCK in the effect of apelin through sensory neurons. Conclusion: Apelin demonstrates the gastroprotective effects in I/R injury by decreasing lesion index, MPO activity, LPO and TNF-α; increasing blood flow, CGRP, NO, and PGE2. The capsaicin sensitive sensory nerves and n. vagus play roles in the protective effect of apelin. Key words: apelin, n.vagus, capsaicin-sensitive afferent nerves, gastric, I/R