nitroarginine and Intestinal-Obstruction

The experiments in this study were designed to follow the time course of nitric oxide (NO) synthesis in the large bowel during acute mechanical ileus.. Occlusion of the mid-transverse colon was maintained for 420 min in anesthetized dogs. Strain-gauge transducers were used to analyze motility changes on the hepatic and lienal flexures, respectively. Constitutive NO synthase (cNOS) and inducible NOS (iNOS) activities were determined in tissue biopsies, and plasma nitrite/nitrate (NOx) level was measured in the portal blood. Following completion of the baseline studies, the animals were treated with either 7-nitroindazole (7-NI, selective neuronal NOS inhibitor), or N-nitro-L-arginine (NNA, non-selective NOS inhibitor).. In the sham-operated group the cNOS activities differed significantly in the oral and aboral tissue samples (oral: 102.9; versus aboral: 62.1 fmol/mg protein/min). The obstruction elicited a significant increase in portal NOx and elevated tissue inducible NO synthase (iNOS) activity. NNA treatment decreased the motility index in both intestinal segments for 60 min, but 120 min later the motility index was significantly elevated (2.5-fold increase in the oral part, and 1.8-fold enhancement in the aboral segment, respectively). Treatment with 7-NI decreased the cNOS activity in the oral and aboral parts by approximately 40% and 70%, respectively, and suppressed the motility increase in the aboral colon segment.. The motility of the colon was either significantly increased or decreased, depending on the type and selectivity of the NOS inhibitor compounds applied. NO of neuronal origin is a transmitter that stimulates peristaltic activity; but an increased iNOS/nNOS ratio significantly moderates the obstruction-induced motility increase.

Topics: Animals; Blood Pressure; Colonic Diseases; Dogs; Enzyme Inhibitors; Gastrointestinal Motility; Intestinal Obstruction; Intestine, Large; Nitrates; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Nitrites; Nitroarginine

The effect of two prostaglandin biosynthesis inhibitors and their interaction with the L-arginine/nitric oxide (NO) pathway was investigated in a rat model of experimental ileus. The gastrointestinal transit was measured as the migration of Evans blue after three different operations. Indomethacin completely reversed the additional inhibition of the transit induced by mechanical stimulation of the gut. Ketorolac completely reversed the inhibition of the transit induced by the laparotomy, but had no additional effect on the inhibition induced by mechanical stimulation of the gut. Administration of indomethacin plus L-nitroarginine or L-arginine could not enhance or prevent the effect of indomethacin alone. Administration of ketorolac and L-nitroarginine completely reversed the transit after the laparotomy plus manipulation whereas ketorolac plus L-arginine had no additional effect as compared to ketorolac alone. From these findings we conclude that in addition to NO, prostaglandins are involved in the pathogenesis of postoperative ileus in the rat. However, indomethacin and ketorolac differentially affect postoperative ileus suggesting that prostaglandins are involved in different pathogenic mechanisms leading to postoperative ileus.

Topics: Animals; Disease Models, Animal; Indomethacin; Intestinal Obstruction; Ketorolac; Nitric Oxide; Nitroarginine; Postoperative Complications; Prostaglandin Antagonists; Rats; Tolmetin

1. In a rat model of experimental ileus, the effect of blockade of adrenergic and nitrergic neurotransmission was studied on the intestinal transit of Evans blue. 2. Ether anaesthesia and skin incision had no influence on the transit. Laparotomy significantly inhibited the transit of Evans blue. This inhibition was even more pronounced when the small intestine was manipulated. 3. Reserpine (5 mg kg-1), a drug that blocks adrenergic neurotransmission, completely reversed the inhibition of the transit induced by laparotomy but only partially reversed that induced by laparotomy with manipulation of the small intestine. 4. N omega-nitro-L-arginine (L-NOARG, 5 mg kg-1), a nitric oxide synthase inhibitor, completely reversed the reserpine-resistant inhibition induced by laparotomy with manipulation of the small intestine. The effect of L-NOARG was prevented by concomitant administration of L-arginine. L-Arginine itself slightly, but significantly enhanced the inhibition. S-methylisothiourea and aminoguanidine, selective inhibitors of the inducible NO synthase, had no effect on the transit after the three operations. 5. Treatment of the rats with reserpine plus L-NOARG had no additional effect on the transit after laparotomy as compared to reserpine alone. However, reserpine plus L-NNA completely reversed the inhibition of the transit induced by laparotomy with manipulation of the small intestine. 6. These findings support the involvement of adrenergic pathways in the pathogenesis of ileus and suggest that the additional inhibitory effect of mechanical stimulation results from an enhanced release of NO by the constitutive NO synthase.

Topics: Adrenergic Antagonists; Adrenergic Uptake Inhibitors; Anesthesia, General; Animals; Arginine; Autonomic Pathways; Enzyme Inhibitors; Gastrointestinal Transit; Guanidines; Intestinal Obstruction; Isothiuronium; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Rats; Rats, Wistar; Reserpine