Intestinal ischemia impairs gastrointestinal motility. The aims of this study were to investigate the effect of intestinal ischemia on gastrointestinal transit and on the expression of enteric transmitters in the rat, and whether the glutamate N-methyl-d-aspartate receptors influence these effects. Ischemia (1 h), induced by occluding the superior mesenteric artery, was followed by 0 or 24 h of reperfusion. Normal and sham-operated rats served as controls. Serosal blood flow was measured with laser Doppler flow meter. Gastrointestinal transit was measured as time of appearance of a marker in fecal pellets. Immunohistochemistry was used to evaluate the number of neurons immunoreactive for neuronal nitric oxide synthase (NOS) or vasoactive intestinal polypeptide and the density of substance P immunoreactive fibers in the myenteric plexus. The N-methyl-d-aspartate receptors antagonist, (+)-5-methyl-10,11-dihydro-5HT-[a,b] cyclohepten-5,10-imine (MK-801) (1 mg/kg i.v.) or the NOS inhibitor, N-nitro-l-arginine (10 mg/kg i.v.) was administered prior to ischemia. Serosal blood flow was decreased by 70% during ischemia, but it was not altered in sham-operated rats. Gastrointestinal transit was significantly prolonged in ischemic/reperfused rats compared with controls. There was a significant increase in the number of vasoactive intestinal polypeptide and neuronal nitric oxide synthase immunoreactive neurons, and a marked decrease of substance P immunoreactive fibers in ischemia followed by 24 h of reperfusion animals compared with controls. These alterations were not observed in ischemia without reperfusion. A significant delay of gastrointestinal transit and increase of vasoactive intestinal polypeptide neurons were also observed in sham-operated rats. The changes in transmitter expression and gastrointestinal transit in ischemic/reperfused rats were prevented by pre-treatment with the NOS inhibitor, N-nitro-l-arginine or the N-methyl-d-aspartate receptors antagonist, MK-801. This study suggests an involvement of the glutamatergic system and its interaction with nitric oxide in intestinal ischemia/reperfusion. Ischemia/reperfusion might induce local release of glutamate that activates N-methyl-d-aspartate receptors leading to increased production of nitric oxide and adaptive changes in enteric transmitters that might contribute to gastrointestinal dysmotility. 相似文献
1. Physalaemin, an endecapeptide recently found in the skin of the South American amphibian Physalaemus fuscumaculatus, possesses, besides a marked hypotensive action and a powerful sialogogic activity, also a stimulant activity on other exocrine secretions.
2. Exocrine structures which were more potently stimulated by the peptide were lacrimal glands and exocrine pancreas. In the anaesthetized dog the threshold lacrimatory dose was 0·05-0·3 μg/kg; in the rat the threshold dose was 2·5-5 μg/kg. The minimum active dose on exocrine pancreas of the dog was 0·05-0·5 μg/kg.
3. Physalaemin did not influence the gastric acid secretion of the dog at the maximum tolerated dose (40 μg/kg). Gastric acid secretion of the rat was stimulated very little if at all.
4. In the dog the peptide caused some changes in the bile flow which were connected more with contracture of the gall-bladder than with a true secretory stimulant activity. In the rat the peptide was completely ineffective.
5. The results obtained after administration of sympatholytic and parasympatholytic agents suggest that the action of the peptide is at least partly independent from the autonomic nervous system.
In a previous screening work, Foeniculum vulgare essential oil emerged from a pool of 24 essential oils for its antiplatelet properties and its ability to destabilize the retraction of the coagulum. In the present work the main component of the oil, anethole, tested in guinea pig plasma was as potent as fennel oil in inhibiting arachidonic acid-, collagen-, ADP- and U46619-induced aggregation (IC(50) from 4 to 147 microg ml(-1)). It also prevented thrombin-induced clot retraction at concentrations similar to fennel oil. The essential oil and anethole, tested in rat aorta with or without endothelium, displayed comparable NO-independent vasorelaxant activity at antiplatelet concentrations which have been proved to be free from cytotoxic effects in vitro. In vivo, both F. vulgare essential oil and anethole orally administered in a subacute treatment to mice (30 mg kg(-1)day(-1) for 5 days) showed significant antithrombotic activity preventing the paralysis induced by collagen-epinephrine intravenous injection (70% and 83% protection, respectively). At the antithrombotic dosage they were free from prohemorrhagic side effect at variance with acetylsalicylic acid used as reference drug. Furthermore, both F. vulgare essential oil and anethole (100 mg kg(-1) oral administration) provided significant protection toward ethanol induced gastric lesions in rats. In conclusion, these results demonstrate for F. vulgare essential oil, and its main component anethole, a safe antithrombotic activity that seems due to their broad spectrum antiplatelet activity, clot destabilizing effect and vasorelaxant action. 相似文献
1 Histamine has a dual action on the in situ gall bladder of the guinea-pig: a spasmogenic and a relaxant effect mediated through H1- and H2-receptor stimulation respectively. 2 The contracturant action, mimicked by 2-(2-aminoethyl) thiazole (a specific H1-receptor agonist), is blocked by mepyramine and the relaxation, mimicked by dimaprit (a specific H2-receptor agonist), is inhibited by cimetidine. 相似文献
The H2-antagonist activity of thiazole derivatives, substituted on position 5 with urea-equivalent groups, has been tested on guinea-pig isolated atria stimulated by dimaprit. By comparing the activities of the 2,5-disubstituted thiazole derivatives with those of the corresponding 2,4-disubstituted derivatives it can be seen that the side-chain position is critical to activity and differently influences activity in the various series. The heteroaromatic ring atom sequence N-C-S-C-side chain is always associated with a low antagonist activity. 相似文献