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

1 This study analyses the neural pathway involved in the modulation of gast ric motor function by stress. 2 Systemic administration of low doses of endotoxin (40 mug kg(-1), i.v.) p revents the increase in gastric tone induced by 2-deoxy-D-glucose (200 mg k g(-1), i.v., 2-DG) in urethane-anaesthetized rats. 3 Functional inhibition of afferent neurones by systemic administration of capsaicin (20 + 30 + 50 mg kg(-1), i.m.) in adult rats prevented the inhibi tory effects of endotoxin. 4 Pre-treatment with the nitric oxide synthase (NOS) inhibitor, N-G-nitro-L -arginine methyl ester (L-NAME), both i.v. (10 mg kg(-1)) and i.c. (200 mug rat (1)), prevented the inhibitory effects of endotoxin on gastric tone in duced by 2-DG. 5 Immunohistochemical studies show Fos expression in the dorsal vagal compl ex (DVC) of the brainstem of 2-DG-treated animals. Peripheral administratio n of endotoxin (40 mug kg(-1), i.p.) increased the number of Fos-immunoreac tive 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 pr evented the increase in Fos expression induced by endotoxin in both nuclei. 6 Endotoxin (40 mug kg(-1), i.p.) increased Ca2+-dependent nitric oxide syn thase (cNOS) activity in the brainstem. Addition of 7-nitroindazole (600 mu M, 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 l ow doses of endotoxin involves activation of capsaicin-sensitive afferent n eurones and neuronal NOS in the brainstem.