VASOINHIBITORY EFFECTS OF NC-1005 AND NC-1006, NEW SYNTHESIZED ANTIARRHYTHMIC AGENTS, IN ISOLATED RAT AORTA

1. NC 1005 and NC 1006 (3 x 10(-6)M-10(-)4 M) inhibited the contractio ns induced by phenylephrine (PE) and KCl in isolated rat aortas with o r without endothelium. 2. In a Ca2+-free medium containing EGTA and ni fedipine, NC 1005 and NC 1006 inhibited PE-response and a subsequent r esponse to Ca2+ in the presence of PE. 3. NC 1005 and NC 1006 also cau sed relaxations of endothelium-removed aortas precontracted with PE. 4 . The relaxations induced by NC 1005 and NC 1006 were potentiated by a miloride, zaprinast and theophylline but not by increasing the externa l Na+ concentration. 5. Methylene blue and ouabain slightly potentiate d NC 1005-relaxation, but not NC 1006-relaxation. 6. Glyburide, apamin e and nifedipine had no effect on the relaxations. 7. NC 1005 and NC 1 006 potentiated the relaxation induced by nitroglycerin (NG) without a ffecting isoproterenol-relaxation. 8. In the presence of forskolin, NC 1005 and NC 1006 failed to potentiate NG-relaxation. 9. These results suggest that the vasoinhibitory effects of NC 1005 and NC 1006 may be due to an increase in the level of cAMP.