VASODILATORY ACTION OF HA1004 [N-(2-GUANIDINOETHYL)-5-ISOQUINOLINESULFONAMIDE], A NOVEL CALCIUM-ANTAGONIST WITH NO EFFECT ON CARDIAC-FUNCTION

Abstract

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 .times. 10-6 M. The isolated guinea pig atria on right ventricular papillary muscles did not respond to HA1004, even at a concentration of 3 .times. 10-4 M. HA1004, like verapamil, produced a competitive inhibition of the Ca2+-induced contraction of the depolarized rabbit aorta. The pA2 value of HA1004 for the Ca2+-induced contraction was 6.60. Atropine, propranolol, theophylline or indomethacin had no effect on the HA1004-induced relaxation. HA1004 (3 .times. 10-6 M) inhibited the contraction produced by Ca2+ ionophore, A23187 [calcimycin], whereas verapamil or diltiazem had no effect on this contraction, even at a concentration of 3 .times. 10-5 M. HA1004 produce a competitive inhibition of Ca2+-induced contraction of the A23187-treated aorta and inhibited the phenylephrine-indued contraction elicited in Ca2+-free solution, thereby suggesting that this drug affects intracellular rather than extracellular Ca2+. Evidently, HA1004 is a novel Ca antagonistic vasodilator with no effect on cardiac function and is apparently of a different class of Ca antagonist from verapamil.