A cerebral nitrergic pathway modulates endotoxin-induced changes in gastric motility

1 This study analyses the neural pathway involved in the modulation of gastric motor function by stress. 2 Systemic administration of low doses of endotoxin (40 m gk g 71 , i.v.) prevents the increase in gastric tone induced by 2-deoxy-D-glucose (200 mg kg 71 , i.v., 2-DG) in urethane-anaesthetized rats. 3 Functional inhibition of aAerent neurones by systemic administration of capsaicin (20+30+50 mg kg 71 , i.m.) in adult rats prevented the inhibitory eAects of endotoxin. 4 Pre-treatment with the nitric oxide synthase (NOS) inhibitor, N G -nitro-L-arginine methyl ester (LNAME), both i.v. (10 mg kg 71 ) and i.c. (200 mg rat 71 ), prevented the inhibitory eAects of endotoxin on gastric tone induced by 2-DG. 5 Immunohistochemical studies show Fos expression in the dorsal vagal complex (DVC) of the brainstem of 2-DG-treated animals. Peripheral administration of endotoxin (40 m gk g 71 , i.p.) increased the number of Fos-immunoreactive cells induced by 2-DG, both in the nucleus tractus solitarii (NTS) and in the dorsal motor nucleus (DMN) of the DVC. Pre-treatment with L-NAME prevented the increase in Fos expression induced by endotoxin in both nuclei. 6 Endotoxin (40 m gk g 71 , i.p.) increased Ca 2+ -dependent nitric oxide synthase (cNOS) activity in the brainstem. Addition of 7-nitroindazole (600 mM, 7-NI) to the assay significantly inhibited the increase in cNOS activity caused by endotoxin. No change in NOS activity of any isoform was observed in the stomach of animals treated with endotoxin. 7 The present study suggests that inhibition of gastric motor function by low doses of endotoxin involves activation of capsaicin-sensitive aAerent neurones and neuronal NOS in the brainstem. British Journal of Pharmacology (2001) 134, 325‐332