Vascular relaxant effects of toborinone on the isolated canine internal mammary artery.

This study was conducted to evaluate the vascular relaxant effects of toborinone on canine internal mammary ring preparations. We determined the concentration-contraction curves for various vasoconstrictors, namely norepinephrine, serotonin, U46619, endothelin-1, phenylephrine, and KCl in internal mammary artery (IMA) preparations, then assessed the vascular relaxant effects of the test drugs. As models, preparations with and without functional endothelium were used. As vasorelaxants, we used milrinone, papaverine, and nitroglycerin. Toborinone produced concentration-dependent relaxation in preparations precontracted with norepinephrine and serotonin. However, the vascular relaxant effect of toborinone on KCl-induced contraction was weaker than those on norepinephrine- and serotonin-induced contraction. Toborinone produced concentration-dependent relaxation in preparations with, and those without functional endothelium. There was no difference in the potency between the preparations with, and those without functional endothelium. The relaxing effect of toborinone on norepinephrine-induced contraction (EC50 = 1.3 x 10(-6) M) was significantly weaker than that of nitroglycerin (EC50 = 7.8 x 10(-8) M), equal to that of papaverine (EC50 = 2.2 x 10(-6) M), and significantly stronger than that of milrinone (EC50 = 3.3 x 10(-6) M). These results demonstrate that toborinone produces relaxant effects on canine IMA preparations, and that it may be effective in the treatment of IMA malperfusion syndrome.