ROLE OF CYCLIC-GMP IN INHIBITORY EFFECTS OF CD-349 IN ISOLATED BLOOD-VESSELS

1. We investigated the effects of CD-349, a dihydropyridine derivative with nitrate ester, on contractile responses induced by high K+, nore pinephrine (NE) and Ca2+ in isolated rabbit aorta. 2. CD-349 (10(-9)-1 0(-5) M) and nifedipine (10(-9)-10(-5) M) equally inhibited the 64 mM KCl-induced contraction of the aortic strips in a concentration-depend ent manner. 8-Br-cyclic GMP (10(-3) M) did not inhibit the KCl-induced contraction of the aortic strips. 3. CD-349 (10(-8)-10(-5) M) and 8-B r-cyclic GMP (10(-6)-10(-3) M) inhibited the 10(-6) M NE-induced contr action of the aortic strips in a concentration-dependent manner. Howev er, nifedipine had no effect on the NE-induced contraction in rabbit a orta. 4. The inhibitory effects of CD-349 on NE-induced contraction we re antagonized by treatment with methylene blue and oxyhemoglobin, whi le they were augmented by treatment with zaprinast. 5. CD-349 (10(-8)- 10(-5) M) and 8-Br-cyclic GMP (10(-5)-10(-4) M) inhibited the NE-induc ed phasic contraction and Ca2+-induced contraction of the aortic strip s preincubated with NE in Ca2+-free medium. However, nifedipine (10(-5 ) M) had little or no effect on both NE-induced phasic contraction and Ca2+-induced contraction of the aortic strips preincubated with NE in Ca2+-free medium. 6. CD-349 (10(-7)-10(-5) M) increased the levels of cyclic GMP in rabbit aorta. 7. These results indicate that CD-349 has a hybrid property deriving from Ca2+-antagonist and cyclic GMP increa sing agents.