We have recently reported that Mg+ +-deficiency showed endothelium dependent relaxation in isolated canine coronary arteries precontracted with PGF2a. To differentiate the release of EDRF or PGI2 from the endothelium cells as the cause of vasorelaxation by Mg + +deficiency, effects of several inhibitors of arachidonic acid metabolism on the relaxation by Mg++deficiency were evaluated and also compared with that of acetylcholine. Ibuprofen and tranylcypromine (10μM), an inhibitor of cyclo-oxyge- , nase and PGI2 synthetase, respectively, did not effect on Mg++free induced vasorelaxation. Pretreatment of quinacrine (10 μM), an inhibitor of phospholipase A2 and also Ca+ + uptake, blocked vasorelaxation by Mg++-free. But trifluoperazine (10μM), which is about as potent as quinacrine in the inhibition of Ca + 4 uptake, did not effect on Mg++deficiency induced vasorelaxation. NDGA (10pM), an inhibitor of lipoxygenase, completely restored Mg+ +-free induced vasorelaxation, even though pretreatment of that was not blocked which might be due to the characteristics of vasorelaxation of NDGA itself. Pretreatment of methylene blue (l0μ M), which is known as a inhibitor of EDRF through the blocking effect of guanylate cyclase, completely blocked vasorelaxation by Mg+ +-free as well as acetylcholine (0.1pM). Acetylcholine-induced dose response curve was also antagonized by pretreatment of quinacrine (10pM), but not by ibuprofen, tranylcypromine and NDGA.
These results appear to suggest that Mg+ +free induced vasorelaxation was mediated by the release of EDRF through the activation of phospholipase A2 and noncyclo-oxygenase on arachidonate metabolism.
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