INHIBITORY EFFECTS OF N-6 AND N-3 HYDROXY FATTY-ACIDS ON THROMBOXANE (U46619)-INDUCED SMOOTH-MUSCLE CONTRACTION

Mammalian platelets are capable of enzymatically producing a number of n-6 and n-3 hydroxy fatty acids. Human platelet suspensions produce t wo major docosahexaenoic acid (22:6n3) metabolites, namely, 11-OH and 14-OH-22:6n3. The hydroxy fatty acids which were formed by human plate lets and purified by high performance liquid chromatography specifical ly antagonize the contractile effects of a thromboxane mimetic, U46619 , in airway, visceral and, especially, in the vascular smooth muscle p reparations studied. The efficacy of OH-22:6n3 (IC25 = 1.1 mu M) was c ompared to other n-6 and n-3 hydroxy fatty acids in the rat aortic rin g preparation. The OH-22:6n3 was significantly more potent with the ex ception of OH-22:5n3. The rank order of their potency was 14-OH-22:5n3 greater than or equal to 14-OH-22:6n3 > 17-OH-22:6n3 greater than or equal to 11-OH-22:6n3 greater than or equal to 11-OH-22:5n3 > 12-OH-20 :5n3 greater than or equal to 12-OH-20:4n6 greater than or equal to 14 -OH-22:5n6 > 13-OH-18:2n6 > 14-OH-22:5n5. Antagonism of thromboxane ef fects may be an important aspect of the biological function of 22-carb on n-3 hydroxylated fatty acids in platelet-vascular smooth muscle cel l interactions.