Effects of the anti-ulcer drug SU-88 on the gastric blood flow and the cardiovascular system

Effects of a newly synthetized anti-ulcer drug, 2'-Carboxymethoxy-4, 4'-bis(3-methyl-2-butenyloxy)chalcone (SU-88), on gastric blood flow and the cardiovascular system were investigated. Intravenously administered SU-88 dose-dependently increased the blood flow of gastric tissues in rats. In anesthetized dogs, i.a. administered SU-88 also increased the short gastric and the femoral arterial blood flows. SU-88 (1 mg/kg, 3 mg/kg and 10 mg/kg i.v.) caused a mild fall in systemic blood pressure, an increase in heart rate, and a stimulation of respiration; however, these effects were only transient and recovered to the basal level within few minutes. No notable changes were observed in the electrocardiogram except for a shortening of the R-R interval accompanied by an increase in heart rate. The blood flow of the common carotid, the vertebral, the coeliac, the superior mesenteric, and the femoral arteries in dogs were all increased by i.v. administration of SU-88, and among them an increase in the coeliac arterial blood flow was prominent. SU-88 increased the perfusates in isolated rabbit ear and relaxed the contraction of isolated rabbit aorta induced by noradrenaline, but showed no influences on the amplitude, heart rate, and coronary flow of isolated rabbit heart. The hypotensive effect of SU-88 was not abolished by i.v. administered atropine, diphenhydramine, and propranolol and not influenced by vagotomy. Intravertebrally administered SU-88 increased the vertebral blood flow, but showed no influence on systemic blood pressure. Furthermore, SU-88 showed no influence on the rise in blood pressure by both common carotid occlusions. The increase in the femoral and the short gastric arterial blood flow induced by i.a. administration of SU-88 was not inhibited by atropine, diphenhydramine, and propranolol and not influenced by pretreatment with aminophylline. These results suggest that the hypsoensive and vasodilative effects of SU-88 are not mediated by the central nervous system, autonomic nervous system, histamine and the action of adenosine augmentation and further experiments are necessary for precise explanations of its mechanism.