L-Arginine, nitric oxide, and intestinal secretion: studies in rat jejunum in vivo (original) (raw)

Abstract

Background-L-Arginine has been shown to induce fluid secretion in human jejunum. Nitric oxide, a derivative of L-arginne is thought to have an important role as an intestinal secretagogue. Aim-To determine the effect of Larginine and the nitric oxide synthase inhibitor, nitro L-arginine methyl ester (L-NAME), on fluid and electrolyte movement in rat jejunum. Methods-A 25 cm segment ofrat jejunum was perfused in situ with iso-osmotic solutions containing either (1) saline, (2) D-arginine 20, (3) L-arginine 20, (4) L-NAME 0-1, 1, or 20 mmol/l, or (5) a combination of L-arginine 20 and L-NAME 0.1, 1, or 20 mmol/l. In further groups the effect of a subcutaneous injection of L-NAME 100 mglkg was examined in rats pretreated with either Dor L-arginine 500 mg/kg. Results-L-Arginine, unlike D-arginine, induced fluid secretion despite being better absorbed (mean-7 3 v 17-0 ,l/min/ g; p<001). L-NAME at 0.1 mmol/l had no effect on basal fluid movement but reversed L-arginine induced secretion (7.8; p<005). L-NAME at 1 and 20 mmol/l induced fluid secretion (-15.4 and-28-4, respectively), which was enhanced by the addition of L-argilnlne (-30.0 and-41-0, respectively; both p<005). A subcutaneous injection of L-NAME resulted in marked fluid secretion (-39.9) and histological evidence of intestinal ischaemia. These changes were attenuated or reversed by pretreatment with subcutaneous L-but not D-arginine. Conclusions-L-Arginine induces intestinal fluid secretion through production of nitric oxide. There is a delicate balance between the effect of nitric oxide as a secretagogue and its effect on maintaining blood flow and thus preventing intestinal ischaemia.

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