Adrenergic control of small intestinal motility and blood flow : an experimental study in rat and man

Abstract: Small intestinal motility in the fasted state is characterized by migrating motor complexes (MMCs). Both animals and man exhibit the MMC, which consists of periods of regular contractions, i.e. activity fronts, that migrate along the length of the small bowel and alternate with periods of quiescence. Animal experiments have demonstrated cyclic changes of intestinal blood flow which parallel muscular contractions. Using a recently developed technique, laser Doppler flowmetry (LDF), which permits registration of gastrointestinal blood flow in man, we designed a new method that simultaneously measures intramural blood flow and intraluminal pressure in the small intestine. Through this method, the relationship between hemodynamics and motility in man was evaluated and the involvement of adrenergic mechanisms in the regulation of intestinal motility and hemodynamics was assessed. In rats, [alpha]2-adrenoceptor agonists were found to inhibit the MMC. In man, peripherally acting [alpha]2-adrenoceptor agonists such as oxyrnetazoline inhibited the MMC, while centrally acting [alpha]2-adrenoceptor agonists, such as clonidine, in contrast were found to stimulate the MMC. [alpha]-Adrenergic agonists reduced intramural blood flow. ß-Adrenoceptor agonists exerted different actions on motility in rats depending on the ß-receptor subtype involved. In particular, ß2-adrenoceptors, but also ß3-adrenoceptors, appeared to subserve a function in the regulation of small intestinal motility by disrupting the regular MMC pattern in rats. In man, a non-selective ß-adrenoceptor agonist induced a motility pattern similar to fed motility. ß-Adrenoceptor agonists increased intramural blood flow. There was a clear relationship between fasting motility and blood flow in the human gut, in which LDF revealed a pattern of changes in blood flow similar to the different phases of MMC, i.e. we observed low perfusion unit (PU) values during phase I, higher PU values during phase II and maximal PU values during phase III. During activity fronts, individual LDF cycles and contraction cycles were phase displaced 180 degrees with [alpha]- and ß-adrenoceptors as important regulators of motility as well as hemodynamics of the small intestine. From this work LDF emerges as a promising tool to study hemodynamics in clinical gastroenterology.