INTRACELLULAR CA++ ANTAGONIST, HA1004 - PHARMACOLOGICAL PROPERTIES DIFFERENT FROM THOSE OF NICARDIPINE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 233  (2) , 454-458
Abstract
Pharmacological properties of N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA1004), a newly synthesized intracellular Ca2+ antagonist, were studied by comparing its cardiovascular actions with those of nicardipine, a Ca2+ entry blocker. Both i.a. and i.v. injections of HA1004 produced a dose dependent increase in vertebral, coronary and renal blood flow, respectively, in pentobarbital-anesthetized dogs. Continuous infusion of atropine, propranolol or aminophylline exerted no significant effect on the HA1004-induced vasodilation. A Ca2+ entry blocker, nicardipine, increased vertebral and coronary blood flow after injections but did not produce an increase in renal blood flow, thereby suggesting notable differences between the cardiovascular effects of HA1004 and the Ca2+ entry antagonist, nicardipine. HA1004 inhibited KCl, phenylephrine and prostaglandin F2.alpha.-induced contraction of isolated canine renal arterial preparations, in a dose-dependent fashion, whereas nicardipine was much less effective in the blocking contraction of the preparation induced by phenylephrine and prostaglandin F2.alpha.. HA1004 inhibited the phenylephrine-induced contraction of the renal artery in the absence of Ca2+. HA1004 neither depressed the amplitude nor the duration of the slow action potentials of isolated guinea-pig hearts. HA1004 is a Ca2+ antagonist of different class from Ca2+ entry blockers such as nicardipine.