Control Of Mucosal Blood Flow Research Articles

Effect of gastrointestinal function regulatory Kampo medicine, Dai-kenchu-to on human plasma calcitonine gene-related peptide, substance P and somatostatin levels

Background Traditional Chinese herbal (Kampo) medicines, Dai-kenchu-to (DKCT) have been frequently used in the empirical treatment of gastrointestinal obstructions. Although it has been already reported that DKCT increases in the plasma levels of gastrointestinal peptides {vasoactive intestinal polypeptides (VIP) and motilin}, which improves feelings of abdominal coldness and gastrointestinal motility, the mechanism is not yet well understood. In this study, we examined effects of DKCT on the plasma calcitonine gene-related peptide (CGRP), substance P (SP) and somatostatin (SS) levels. Methods DKCT or placebo was orally administered to five healthy male volunteers aged 25–30 years. Venous blood samples were taken before and 20, 40, 60, 90, 120, 180 and 240 min after administration of DKCT. Peptide levels in plasma were measured using a sensitive enzyme immunoassay. Results DKCT (7.5 g) significantly increased in CGRP-like immunoreactive substances (IS) at 40 min, SP-IS at 20–60 min and SS-IS at 180–240 min compared with the each response of placebo. Conclusions In this study, DKCT raised plasma CGRP-, SP- and SS-IS levels. CGRP and SP participate in the control of mucosal blood flow in the gastrointestinal tract. Also, SS participates in the regulation of gastrointestinal motility. DKCT might regulate to the mucosal blood flow by increasing in plasma CGRP- and SP-IS levels. Besides, DKCT might improve the gastrointestinal motility by increasing in plasma SS-IS levels. Clinical Pharmacology & Therapeutics (2005) 77, P13–P13; doi: 10.1016/j.clpt.2004.11.052

Neural reflexes controlling intestinal microcirculation.

It has long been established that neural reflexes are involved in the regulation of gastrointestinal vascular function, in particular the mucosal hyperemia that follows food ingestion. However, more precise identification of reflex pathways involved in the control of mucosal blood flow had not previously been forthcoming because of a lack of adequate methods to examine resistance arterioles within the intestinal wall. Recent advances have employed novel in vitro preparations and videomicroscopic techniques to investigate the neural control of the gastrointestinal microvasculature and involvement of intrinsic and extrinsic vasodilatory neurons in mucosal reflexes. Vasoconstrictor innervation to submucosal arterioles is mediated solely by extrinsic sympathetic nerves that release ATP onto arteriolar P2n-purinoceptors. Neurogenic vasodilation of submucosal arterioles occurs by release of acetylcholine and/or neuropeptides from intrinsic submucosal neurons as well as by release of substance P and calcitonin gene-related peptide from extrinsic sensory nerves. Both vasodilator pathways can be activated independently by mucosal stimulation, and both have afferent and efferent components confined to the mucosa and submucosal neuronal plexus. We speculate that the intrinsic enteric cholinergic reflex pathways are involved in local physiological control of mucosal blood flow, whereas extrinsic sensory reflex pathways are preferentially activated during inflammatory states.

Prostaglandins in pathophysiology of peptic ulcer disease.

Gastric ulcer (GU) and duodenal ulcer (DU) occur as a result of the imbalance between aggressive and defensive factors affecting the gastroduodenal mucosa. Prostaglandins (PG) of E and I series are generated throughout the gastrointestinal tract, particularly in the gastric and duodenal mucosa, and are released into the gut lumen upon vagal and hormonal stimulation. Endogenous PGs may be involved in the maintenance of mucosal integrity, control of mucosal blood flow and protection against potentially noxious agents. Gastric mucosa of ulcer patients tends to generate smaller amounts of PGs of E and I series and exhibits a reduced ratio of PG to thromboxane generation, which suggests that the deficiency of protective PG may play a role in the pathogenesis of peptic ulcer. Suppression of mucosal generation of PGs by non-steroidal anti-inflammatory compounds causes mucosal damage and increases the risk of the formation or exacerbation of peptic ulcer. Exogenous PGE and its stable analogs have been tested successfully in the treatment of GU and DU and the results so far obtained indicate that these agents significantly increase the ulcer healing rate. Certain anti-ulcer drugs such as carbenoxolone, sucralfate, colloidal bismuth and cimetidine appear to exert their beneficial effects on ulcer healing by mediating the release of endogenous PGs.

Histamine receptor control of gastric microvasculature in shock

Control of gastric mucosal blood flow in hemorrhagic shock was investigated, in an anesthetized miniature swine model, using H 1-receptor (diphenhydramine) and H 2-receptor (cimetidine) antagonisms. The animals were divided into two experimental groups: (i) diphenhydramine treatment; and (ii) diphenhydramine plus cimetidine treatment. Results were compared to previously reported untreated controls and animals who received cimetidine alone. Conclusions reached were: (1) Histamine receptors in the gastric microvasculature do play a role in the control of mucosal blood flow during shock. (2) H 2-Receptor antagonism, whether alone or in conjunction with H 1-receptor antagonism, results in significant protection against a shock-related decrease in gastric mucosal blood flow. (3) H 1-Receptor antagonism does not affect gastric mucosal blood flow in shock.