BIPHASIC RESPONSES OF EQUINE COLONIC VESSEL RINGS TO VASOACTIVE INFLAMMATORY MEDIATORS

1 The role of endothelium in modulating equine colonic vessel response s to histamine (HST), 5-hydroxytryptamine (5-HT), bradykinin (BK) and acetylcholine (ACh) was evaluated in vitro. 2 Segments of mesenteric a rteries and veins were collected from the left ventral colon of six ad ult horses destined for euthanasia for reasons unrelated to cardiovasc ular or gastrointestinal systems. Vessels were gently cleansed and cut into 4 mm wide rings. 3 Three vessel conditions namely endothelium in tact, endothelium removed and N-omega-nitro-L-arginine methyl ester (L -NAME)-treated were used for both arterial and venous rings. Each ring was placed in an organ bath with oxygenated Tyrode's solution. One si de of the ring was fixed to the floor of the bath and the other side t o a force-displacement transducer interfaced with a polygraph. 4 An in itial tension of 2 g was applied to rings which were allowed to equili brate for 45 min. The bath solution was gently replaced every 15 min a nd tension was readjusted to 2 g each time except following the last w ash. 5 Rings were precontracted with a single ECU dose of noradrenalin e and after the response plateaued, cumulative concentration (10(-1)2- 10(-4) M) response curves were determined for each agent on separate r ings. The relaxation from the precontracted level to the baseline was considered as 100% relaxation. Maximal relaxation and maximal contract ions were statistically analyzed. 6 All agents induced a relaxation re sponse initially, followed by a contractile phase as the concentration s increased in both arteries and veins, thus, making a biphasic concen tration-response curve. In arteries, relaxation produced by ACh was si gnificantly greater than S-HT. Endothelium removal and L-NAME treatmen t significantly reduced relaxation in arteries. Only endothelium remov al produced a significant reduction of relaxation in veins. 7 In both arteries and veins, I-IST and 5-HT produced significantly greater cont raction than ACh or BK. No significant change in contraction was obser ved in arteries either by endothelium removal or L-NAME treatment, how ever, contraction was significantly reduced in veins by endothelium re moval. 8 These findings suggest that the endothelium plays a major rol e in modulating equine colonic arterial relaxation via nitric oxide an d venous contraction via endothelium-derived contractile mediators, pr obably endothelin and/or arachidonates.