Cytoprotective Action of L-Arginine against HCl-Induced Gastric Injury in Rats: Involvement of Nitric Oxide?

Abstract

ABSTRACT-We examined the cytoprotective effect of L-arginine on gastric damage induced by 0.6 N HC1 in rats and investigated whether the mechanism of this action is related to the nitric oxide (NO)-mediated protection. The animals were given 0.6 N HCI by gavage and killed 1 hr later. L-Arginine (100, 300 and 750 mg/kg) given p.o. 30 min before HC1 treatment prevented these lesions in a dose-dependent manner, but had no effect when given i.v. (200 mg/kg). Similar effects were observed by D-arginine but not by an equimolar dose of mannitol. This effect of L-arginine (p.o.) was attenuated significantly by prior administra tion of indomethacin (5 mg/kg, s.c.) but not by NG-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg, i.v.), the NO synthase inhibitor. Both L and D-arginine produced a reduction in potential difference (PD), inhibi tion of gastric motility, and increases of luminal pH and mucosal blood flow when they were given intra gastrically. Indomethacin significantly mitigated these changes induced by L-arginine except PD reduction, while L-NAME showed significant inhibition only against the increased pH response. We conclude that L arginine given p.o. exhibits gastric cytoprotection against HCl-induced damage in rats, probably by acting as a mild irritant. The mechanism of this action may appear through "adaptive cytoprotection" mediated by endogenous prostaglandins and does not involve the NO-mediated protective pathway.

Role of Nitric Oxide in Pathogenesis of Aspirin-Induced Gastric Mucosal Damage in Rats

“…The increase of GMBF by ASA has been also reported in rats subjecting to cold exposure, despite potentiating the ulcerogenic response in the stomach [22]. In the present study, we also confirmed our previous observation that L-NAME did not reduce but caused a temporal increase of GMBF under urethane anesthetized conditions [23]. Tepperman and Whittle [24] reported significant decrease of GMBF after administration of L-NAME in pentobarbital-anesthetized rats, while Lippe and Holzer [25] reported that inhibition of NO synthesis failed to alter basal GMBF in the rats anesthetized with urethane.…”

Gastrointestinal Function Regulation by Nitrergic Efferent Nerves

“…The protective action of L-arginine against chronic gastric ulcer in rats appears to involve gastric hyperemia mediated by NO, and the ulcer healing properties of L-arginine may depend upon its hyperemic and angiogenic actions, possibly involving NO (Brzozowski et al, 1997). On the other hand, the cytoprotective effect 330 TODA AND HERMAN of L-arginine against HCl-induced gastric injury in rats invokes endogenous prostaglandins rather than NO (Takeuchi et al, 1993). Copious diarrhea produced following the oral administration of castor oil to rats was inhibited or prevented by L-NMMA or L-NAME by decreasing the intestinal fluid accumulation and Na ϩ secretion, suggesting that endogenous NO participates in castor oil-induced diarrhea (Mascolo et al, 1993).…”

Recent Advances in Gastrointestinal Pathophysiology: Role of Heat Shock Proteins in Mucosal Defense and Ulcer Healing.

“…26) It has been reported that an increase in gastric mucosal blood flow is observed after treatment with mild irritants 32) and that inhibition of the increase in mucosal blood flow by indomethacin, N G -nitro-L-arginine methyl ester (L-NAME), or sensory ablation, aggravates mucosal lesions resulting from strong irritants. [32][33][34] Based on such evidence, the mucosal microcirculation is believed to play an important role in mucosal protection by removing back-diffused acid in the mucosa and transporting humoral factors involved in cytoprotection into the epithelial cells. It has been suggested that gastric motility changes play a role in the development and prevention of gastric lesions following both stress and administration of nonsteroidal anti-inflammatory drugs.…”