Effects of trimebutine maleate (TM) on intestinal motility in short bowel syndrome (SBS) were studied in conscious canines in both acute and chronic phases following 80% massive distal small bowel resection (MSBR). TM was administered orally to beagles with MSBR or as controls in the postprandial and fasting states, and given simultaneously with meals. Intestinal motility was measured using bipolar electrodes for approximately 1 month after the electrodes were implanted in each beagle and the data compared between treatment groups. When TM was given with meals, the postprandial period without duodenal migrating myoelectric (or motor) complexes (MMCs) was shorter than in those given meals only. When TM was given in the postprandial state in short bowel beagles, the initial duodenal MMCs occurred earlier, i, e, the postprandial period was shorter. Diarrhea did not occur in these beagles. When TM was given in the fasting state, duodenal MMCs occurred and propagated to the distal intestine. In conclusion, oral TM administration can produce a more appropriate Intestinal condition for the next food intake and make enteral nutrition possible even in the acute phase after MSBR. Such feeding can be carried out without overloading gut function as a result of the modulation of gastrointestinal motility by TM.

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Endothelial factors involved in the bradykinin (BK)-induced relaxation of the guinea-pig aorta were investigated using isolated aortic rings. In intact aortic rings, higher concentrations of BK (≥10^-7M) produced contraction, possibly as a direct action on smooth muscle. This BK-induced contraction was enhanced either by N^ω-nitro-L-arginine (NOLA), an inhibitor of the production of nitric oxide or by indomethacin (IND), an inhibitor of cyclooxygenase, but not by carbenoxolone (CX), a known inhibitor of gap junctions. In aortic rings contracted with noradrenaline, BK elicited a relaxation with two components ; an initial fast relaxation followed by a gradually diminishing slow relaxation, both in an endothelium-dependent manner. The BK-induced relaxation was inhibited in a drug specific manner by either NOLA, IND or CX. NOLA either abolished the fast relaxation, or sometimes converted it into a contractile response. IND reduced the amplitude and duration of the relaxation, by inhibiting the fast relaxation and abolishing the following slow relaxation. CX reduced both components of the relaxation. In the presence of both NOLA and CX, the BK-induced relaxation was converted to a contractile response followed by an IND-sensitive slow relaxation. In the presence of NOLA and IND together, BK stimulation caused a contraction with no following relaxation. These results indicate that in aortic rings of the guinea-pig, BK stimulates endothelial cells to release nitric oxide and prostanoids that produce the fast and slow components of the relaxation respectively. The effects of CX suggest that the contribution of EDHF to the BK-induced relaxation is weak.

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Hepatic arteries are reportedly innervated by vasoconstrictor and vasodilator nerves. Experiments were carried out to investigate the possible involvement of calcitonin gene related peptide (CGRP) and nitric oxide as neurotransmitters during the relaxation of the rat common hepatic artery produced by transmural electrical field stimulation (ES). Common hepatic arteries were excised under ether-anesthesia from 6 weeks-old female rats, and isometric tensions recorded from endothelium-damaged ring preparations. In the presence of atropine and guanethidine, ES relaxed arteries which had been previously contracted with vasopressin. The relaxation response to ES was attenuated by either tetrodotoxin or capsaicin-pretreatment. CGRP induced a concentration-dependent relaxation, which was inhibited by the CGRP antagonist CGRP_8-37. The ES-induced relaxation was attenuated either slightly by the nitric oxide synthesis inhibitor L-nitroarginine (L-NNA) or markedly by CGRP_8-37. The relaxation response was nearly abolished in the presence of both CGRP_8-37 and L-NNA. These results may indicate that the nerve stimulation-induced vasodilatation of the rat common hepatic artery is mediated mainly by CGRP and partly by nitric oxide.

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