Biphasic responses of equine colonic vessel rings to vasoactive inflammatory mediators

1. The role of endothelium in modulating equine colonic vessel responses to histamine (HST), 5-hydroxytryptamine (5-HT), bradykinin (BK) and acetylcholine (ACh) was evaluated in vitro. 2. Segments of mesenteric arteries and veins were collected from the left ventral colon of six adult horses destined for euthanasia for reasons unrelated to cardiovascular or gastrointestinal systems. Vessels were gently cleansed and cut into 4 mm wide rings. 3. Three vessel conditions namely endothelium intact, 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 side of the ring was fixed to the floor of the bath and the other side to a force-displacement transducer interfaced with a polygraph. 4. An initial tension of 2 g was applied to rings which were allowed to equilibrate for 45 min. The bath solution was gently replaced every 15 min and tension was readjusted to 2 g each time except following the last wash. 5. Rings were precontracted with a single EC25 dose of noradrenaline and after the response plateaued, cumulative concentration (10(-12)-10(-4) M) response curves were determined for each agent on separate rings. The relaxation from the precontracted level to the baseline was considered as 100% relaxation. Maximal relaxation and maximal contractions were statistically analyzed. 6. All agents induced a relaxation response initially, followed by a contractile phase as the concentrations increased in both arteries and veins, thus, making a biphasic concentration-response curve. In arteries, relaxation produced by ACh was significantly greater than 5-HT. Endothelium removal and L-NAME treatment significantly reduced relaxation in arteries. Only endothelium removal produced a significant reduction of relaxation in veins. 7. In both arteries and veins, HST and 5-HT produced significantly greater contraction than ACh or BK. No significant change in contraction was observed in arteries either by endothelium removal or L-NAME treatment, however, contraction was significantly reduced in veins by endothelium removal. 8. These findings suggest that the endothelium plays a major role in modulating equine colonic arterial relaxation via nitric oxide and venous contraction via endothelium-derived contractile mediators, probably endothelin and/or arachidonates.