Inhibitory effects of TYB 3823, a new antiarrhythmic agent, on mechanical responses in the vascular smooth muscles.
1. TYB 3823 (3 x 10(-5) M to 10(-3) M) but not lidocaine (10(-4) M) inhibited the contractile response to norepinephrine in rabbit aorta in a competitive manner. On the other hand, TYB 3823 had no effect on contractile responses to histamine, 5-hydroxytryptamine, high KCl and Ca2+. 2. In rabbit aorta, TYB 3823 (10(-5) M and 10(-4) M) but not lidocaine (10(-4) M) also antagonized the ouabain-induced contraction and this action was less potent than that of phentolamine (10(-6) M). 3. In rabbit coronary arteries precontracted with KCl (40 mM), either TYB 3823 or lidocaine inhibited the isoproterenol-induced relaxation to the same levels. Propranolol at 10(-8) M shifted the relaxation curve for isoproterenol to the right and at 10(-6) M it almost completely prevented the relaxation. Further, the effect of a combined treatment with propranolol (10(-8) M) and TYB 3823 (3 x 10(-5) M) was not different from that of a single treatment with propranolol (10(-8) M). 4. In rabbit iliac arteries, TYB 3823 (3 x 10(-5) M and 10(-4) M) but not lidocaine (10(-4) M) suppressed the contractile response to caffeine in a Ca2+-free medium with EGTA and nifedipine. Nitroglycerin (10(-4) M) also inhibited the response but this action was less potent than that of TYB 3823. The combined treatment of the tissue with TYB 3823 and nitroglycerin (both 10(-4) M) further inhibited the responses to caffeine as compared to a single treatment with each drug. 5. These results suggested that TYB 3823 may interfere with the responses due to the mobilization of intracellular Ca2+ activated by caffeine and also has both alpha- and beta-adrenoceptor blocking actions on the vascular smooth muscles.
Shibata
S
S
Department of Pharmacology, School of Medicine, University of Hawaii, Honolulu 96822.
Satake
N
N
Morikawa
M
M
Kodama
I
I
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D007083:Iliac Artery / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D014665:Vasodilator Agents; C059816:restacorin; D012701:Serotonin; D002110:Caffeine; D011189:Potassium Chloride; D006632:Histamine; D002118:Calcium; D009638:Norepinephrine