Vasodilatory action of HA1004 [N-(2-guanidinoethyl)-5-isoquinolinesulfonamide], a novel calcium antagonist with no effect on cardiac function.

A novel compound, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004) was found to be a potent relaxant of blood vessels. Rabbit aortic strips contracted by 18 mM KCl relaxed in the presence of HA1004, with an ED50 value of 2.2 X 10(-6) M. The isolated guinea-pig atria on right ventricular papillary muscles did not respond to HA1004, even at a concentration of 3 X 10(-4) M. HA1004, like verapamil, produced a competitive inhibition of the Ca++-induced contraction of the depolarized rabbit aorta. The pA2 value of HA1004 for the Ca++-induced contraction was 6.60. Atropine, propranolol, theophylline or indomethacin had no effect on the HA1004-induced relaxation. HA1004 (3 X 10(-6) M) inhibited the contraction produced by Ca++ ionophore, A23187, whereas verapamil or diltiazem had no effect on this contraction, even at a concentration of 3 X 10(-5) M. Moreover, HA1004 produced a competitive inhibition of Ca++-induced contraction of the A23187-treated aorta and inhibited the phenylephrine-induced contraction elicited in ca++-free solution, thereby suggesting that this drug affects intracellular rather than extracellular Ca++. The present findings indicate that HA1004 is a novel calcium antagonistic vasodilator with no effect on cardiac function and is apparently of a different class of calcium antagonist from verapamil.