Interactions between the vascular peptide endothelin‐1 and sensory neuropeptides in gastric mucosal injury

Abstract

1 The interactions between endogenous and exogenous sensory neuropeptides on gastric mucosal injury induced by endothelin-1 (ET-1) have been investigated in the anaesthetized rat. 2 Close intra-arterial infusion of ET-1 (4–20 pmol kg⁻¹ min⁻¹) dose-dependently induced vasocongestion and haemorrhagic necrosis in the gastric mucosa. 3 Capsaicin-pretreatment, two weeks earlier to deplete sensory neuropeptides from primary afferent neurones, augmented the mucosal damage induced by ET-1, as assessed by both macroscopic and histological examination. 4 The damage induced by threshold doses of ET-1 alone or in capsaicin-pretreated rats was further enhanced by administration of indomethacin (5 mg kg⁻¹, i.v.), indicating a modulatory influence of endogenous prostanoids. 5 Morphine administration (3 mg kg⁻¹, i.v.), which can prevent neuropeptide release, augmented the damage induced by threshold doses of ET-1, this effect being reversed by naloxone (1 mg kg⁻¹, i.v.). 6 Concurrent local intra-arterial infusion of rat α-calcitonin gene-related peptide (10–50 pmol kg⁻¹ min⁻¹) dose-dependently reduced the mucosal injury induced by ET-1. 7 These findings suggest interactions between ET-1 and sensory neuropeptides, which may reflect an important influence of these peptide mediators in the regulation of mucosal integrity.