THE ACUTE EFFECTS OF HYDRO-ALCOHOLIC KHAT (CATHA EDULIS FORSK) EXTRACT ON MESENTERIC BLOOD FLOW VELOCITY IN GUINEA PIGS. Zewdu Minwuyelet Gebremariam Biomedical department, college of medicine and health sciences, Dilla university, Ethiopia Original Research Paper Physiology INTRODUCTION The chemical constituents of khat have been studied since the late 19th century. Fluckiger and Gerok were among the first who found an alkaloidal fraction in this plant and called it “katin”. This was followed by the isolation of many other substances and it was not known until the year 1975. The most important component of khat was isolated and named Cathinone {S (-)-alpha-aminopropiaphenone)} at the United Nations Laboratories and it is considered the principle stimulant of the central nervous system (United Nations Narcotic Laboratory, 1975). The psycho stimulant component of khat which is Cathinone released within 15–45 min during chewing (Graziani et al., 2008). Following this, the user can experience an increase in blood pressure and heart rate, anorexia, insomnia, alertness, elevated mood and loquacity (Al- Mamary et al., 2002). Furthermore, chronic khat chewing for many years results in unpleasant effect of cognitive defects and psychosis associated with severe neurological illness. Cathinone has a releasing effect on noradrenalin storage sites, which supports the conclusion that Cathinone facilitates noradrenalin transmission. Drake (1988) also proposed that Cathinone and Cathine cause inhibition of noradrenalin uptake. All abused central nervous system stimulants also stimulate the cardiovascular system. Chewing of khat has been associated with a transient rise in blood pressure and heart rate in experimental studies. Regular chewing of khat is associated with elevated mean diastolic blood pressure, which is consistent with the peripheral vasoconstrictor effect of Cathinone (Al Motarreb et al., 2002; Kalix et al., 1991; Hassan et al., 2000). Cathinone (0.5 mg base/kg of body weight) has been associated with a transit increase in blood pressure which its effects coinciding with the presence of Cathinone in blood plasma (Brenneisen et al., 1990; Kalix et al., 1991). These effects could be blocked by the beta1- adrenoreceptor blocker atenolol, but not by the alpha1-adrenoreceptor blocker indoramine, indicating mediation through stimulation of beta1-adrenoreceptor (Hassan et al., 2005). Other studies have found the same increases in blood pressure but also significant increases in heart rate (Hassen et al., 2005). Blood flow around the circulation is driven by a difference in pressure between the arteries and the veins. The amount of blood flow produced for a given pressure gradient depends on how much resistance to flow is offered by the vascular system (Silverthorn, 2009). Blood is an incompressible fluid, and its volume cannot decrease when the ventricles contract. Instead, blood is pressurized, creating the potential energy for blood flow. Blood pressure decreases over distance as potential energy is lost through friction between blood and blood vessel walls and between blood cells. The difference in pressure between the two ends of the vessel, not the absolute pressure in the vessel that determines rate of flow (Guyton and Hall, 2006). Physiologic control of vascular resistance is achieved by altering the blood vessel diameter through vasoconstriction and vasodilatation. The sympathoadrenal system is active to a certain degree (even when at rest) helps to set the “tone” of vascular smooth muscles. Adrenergic sympathetic fibers (release nor epinephrine) activate alpha-adrenergic receptors to cause a basal level of vasoconstriction. Thus, Stimulation of the sympathoadrenal system increases the total peripheral resistance. Parasympathetic endings in arterioles are always cholinergic and promote vasodilation. Parasympathetic innervations of blood vessels are limited to the digestive tract, external genitalia, and salivary glands. Net vascular tone in the mesenteric vasculature is under the influence of several key factors. These factors include locally acting and circulating hormones, intrinsic myogenic properties of the vessel, as well as neurotransmitters released from perivascular post- ganglionic sympathetic neurons. In general, the arteries and veins of the splanchnic circulation are richly innervated with sympathetic nerves that act to constrict these vessels. Maximal activation of the sympathetic constrictor nerves can produce an 80% reduction in blood flow to the splanchnic region. On the other hand, an adequate amount of blood supply is necessary for the proper functioning of all body This in vivo random experimental animal study was conducted to evaluate the acute effects of crude Catha edulis extract on mesenteric blood flow velocity in guinea pigs. A total number of 10 guinea pigs were used. Superior mesenteric blood flow velocity was measured by Ultrasound Doppler flow meter. This was tested by placing its flow meter probe (4 Hz) between 45 and 60 degrees on superior mesenteric blood vessels. Blood flow velocity was recorded digitally for half an hour following normal saline administration as baseline; while 0.2ml Catha edulis extract solution infusion as treatment and recorded for 1hour. Results showed significant increased systolic and diastolic blood flow velocities in response to Catha edulis extract infusion as compared to the base line. The significant increased systolic and diastolic blood flow velocities and the corresponding increase in resistance in superior mesenteric blood vessels in guinea pigs enable us to conclude that khat chewing could decrease the volume of blood flow to the gastrointestinal system. ABSTRACT KEYWORDS : Catha edulis, blood flow velocity, Volume-7 | Issue-11 | November-2017 | 4.894 ISSN - 2249-555X | IF : | IC Value : 79.96 INDIAN JOURNAL OF APPLIED RESEARCH 265 Tesfaye Tolossa Dugul Department of Physiology, College of Medicine and Health sciences, Addis Ababa University, Ethiopia Diresbachew Haile Wendimu Department of Physiology, College of Medicine and Health sciences, Addis Ababa University, Ethiopia Vempati Poornodai Biomedical department, college of medicine and health sciences, Dilla university, Ethiopia Vulli Venkata Rao Department of Biochemistry, Kampala International University- Health Sciences, Dar es Salaam, Tanzania Suberu Safiu Adewale Department of Biochemistry, Kampala International University- Health Sciences, Dar es Salaam, Tanzania