Volume 120, Number 3, Page 464

British Journal of Pharmacology

23 January 1997, Volume 120, Issue 3, Pages 464 – 468

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Article

Effect of adrenergic and nitrergic blockade on experimental ileus in rats
Benedicte Y. De Winter¹, Guy E. Boeckxstaens², Joris G. De Man¹, Tom G. Moreels¹, Arnold G. Herman¹ & Paul A. Pelckmans^1,3
¹Division of Gastroenterology and Pharmacology, Faculty of Medicine, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium     ²Division of Gastroenterology and Hepatology, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

³Author for correspondence

Keywords

Intestinal transit;   nitric oxide synthase;   ileus;   adrenergic pathways;   NANC (non-adrenergic non-cholinergic)

Abstract

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-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.

Received 12 August, 96; Revised 7 October, 96; Accepted 21 October, 96