ABSTRACT-We examined the effects of -2-furanyl]methyl]-amino]ethyl] -2-imidazolidinylidene}propanedinitrile fumarate), a novel gastroprokinetic agent, on gastric mucosal blood flow (GMBF) in anesthetized rats. Intravenous infusion of KW-5092 (0.1 mg/kg/min for 30 min), which did not affect the basal GMBF, reversed the norepinephrine (1 pg/kg/min, i.v. infusion for 30 min)-induced decline of GMBF in the corpus and the antrum. The improvement by KW-5092 of the GMBF was abolished by atropine (0.1 mg/kg/min, i.v. infusion for 30 min). These results suggest that KW-5092, via cholinergic activation, could counteract the decline of GMBF induced by adrenergic activation.Keywords: KW-5092, Gastric mucosal blood flow, NorepinephrineGastric mucosal blood flow (GMBF) is reduced by exogeneous norepinephrine (NE) (1) as well as by sympathetic nerve stimulation (2). In contrast, GMBF is increased by vagal nerve stimulation (3). The increased GMBF following vagal nerve stimulation is counteracted by NE (3), suggesting a counter-regulatory mechanism for the control of GMBF via the sympathetic (adrenergic) and the parasympathetic (cholinergic) nervous system.fumarate) is a newly synthesized gastroprokinetic agent, which enhances gastrointestinal motilities in a wide range from the stomach to the colon (4, 5). In the guinea pig ileum, KW-5092 enhances acetylcholine (ACh) release from enteric neurons (6) and inhibits acetylcholinesterase (AChE) (7). Since KW-5092 stimulates cholinergic activity, it seemed of interest to examine the effects of this drug on the GMBF. In the present study, we investigated the effects of KW-5092 on the basal GMBF and on the decreased GMBF induced by NE in anesthetized rats.Male Sprague-Dawley rats (Japan SLC, Inc., Hamamatsu), weighing 150 to 200 g, were used for the experiment. The animals were maintained on ordinary laboratory chow and tap water ad libitum under a constant 12-hr light-dark cycle. The drugs used were KW-5092, NE and atropine. KW-5092 was synthesized in our laboratories. NE and atropine sulfate were purchased from Sankyo Co., Ltd. (Tokyo) and Nacalai Tesque, Inc.(Kyoto), respectively. The test drugs were dissolved in saline and intravenously infused to rats at a volume of 0.1 ml/kg/min. GMBF was determined according to the reported procedure (8). The animals were deprived of food 24 hr prior to the experiment but allowed free access to water. Each animal was anesthetized by urethane (1.25 g/kg, s.c.), and a polyethylene tube was placed into the trachea for the maintenance of respiration. For the measurement of blood pressure and the i.v. infusion of drugs, polyethylene tubes were placed into the carotid artery and the jugular vein, respectively. The body temperature was maintained at 37±1V with a temperature controller (CMA/150; Carnegie Medicine, Stockholm, Sweden). After a midline incision, the stomach was exposed, and the great curvature was incised. Thereafter, the fiber-opic probe of the laser flowmetry system (ALF21; Advance Co., Ltd., Tokyo) was gently placed on the mucosa of th...