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Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat
Author(s) -
Whittle B.J.R.,
LopezBelmonte J.,
Moncada S.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12977.x
Subject(s) - capsaicin , nitric oxide , prostacyclin , omega n methylarginine , neuropeptide , pharmacology , endogeny , chemistry , substance p , nitroarginine , sodium nitroprusside , nitric oxide synthase , endocrinology , medicine , receptor , biochemistry
1 The interactions between nitric oxide (NO), prostacyclin and sensory neuropeptides in the maintenance of gastric mucosal integrity have been investigated in the anaesthetized rat. 2 Administration of either N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA) to inhibit endothelium‐derived NO formation, indomethacin to inhibit prostanoid biosynthesis or chronic capsaicin pretreatment to deplete sensory neuropeptides, did not induce acute mucosal injury. 3 In capsaicin‐pretreated rats, however, l ‐NMMA (12.5–100 mg kg −1 i.v.) dose‐dependently induced acute mucosal damage, characterized as vasocongestion and haemorrhagic necrosis. The enatiomer d ‐NMMA (100 mg kg −1 i.v.) did not induce any detectable mucosal damage. 4 This mucosal injury induced by l ‐NMMA was inhibited by concurrent administration of l ‐arginine (300 mg kg‐ 1 i.v.). 5 In indomethacin (5 mg kg −1 i.v.)‐pretreated rats, l ‐NMMA also induced mucosal damage. Furthermore, following indomethacin administration in capsaicin‐pretreated rats, l ‐NMMA induced widespread, severe haemorrhagic necrotic damage. 6 These findings suggest a role for endogenous NO formed from l ‐arginine, acting in concert with prostacyclin and sensory neuropeptides, in the modulation of gastric mucosal integrity.