ACTIONS OF DIASPIRIN CROSS-LINKED HEMOGLOBIN ON ISOLATED RAT AND DOG VESSELS

The objectives of these studies were to investigate the responses of i solated blood vessels from rats and dogs to the administration of dias pirin cross-linked hemoglobin (DCLHb) and to determine the mechanisms of these responses. Isolated vascular rings (3 to 5 mm) were suspended at optimal passive tension in Krebs-filled (37 degrees C) tissue bath s and bubbled with 95% O-2-5% CO2, and isometric tension was recorded. With the vessels under basal conditions increasing concentrations of DCLHb (10(-8)-3 x 10(-6) mol/L) were added. DCLHb addition was repeate d during a submaximal contraction with norepinephrine and again during acetylcholine relaxation. The effects of the nitric oxide synthase in hibitor L-nitro arginine (10(-5) mol/L) on the responses to DCLHb were also determined. Dog vessels developed very little tension (1% to 5% of norepinephrine maximum), whereas rat arteries contracted between 9% and 15% when exposed to DCLHb under basal conditions. However, both t he dog and rat vessels developed significant tension to DCLHb when the y were precontracted (5% to 54%) and also when they were relaxed with acetylcholine (21% to 93%). L-nitro arginine eliminated the contractil e responses to DCLHb but did not cause contraction of any of the vesse ls under basal conditions. We conclude that in this model the mechanis m of DCLHb-induced contractions of in vitro dog and rat vessels is dep endent on interference with nitric oxide. This is similar to the mecha nism of DCLHb action in isolated pig vessels reported previously. Diff erences in responses of dog, rat, and pig vessels under basal conditio ns in vitro are the result of active generation of nitric oxide by pig but not by dog or rat vessels.