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 contractions induced by phenylephrine (PE) and KCl in isolated rat aortas with or without endothelium. 2. In a Ca(2+)-free medium containing EGTA and nifedipine, NC 1005 and NC 1006 inhibited PE-response and a subsequent response to Ca2+ in the presence of PE. 3. NC 1005 and NC 1006 also caused relaxations of endothelium-removed aortas precontracted with PE. 4. The relaxations induced by NC 1005 and NC 1006 were potentiated by amiloride, zaprinast and theophylline but not by increasing the external Na+ concentration. 5. Methylene blue and ouabain slightly potentiated NC 1005-relaxation, but not NC 1006-relaxation. 6. Glyburide, apamine and nifedipine had no effect on the relaxations. 7. NC 1005 and NC 1006 potentiated the relaxation induced by nitroglycerin (NG) without affecting 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.
Satake
N
N
Department of Pharmacology, University of Hawaii, School of Medicine, Honolulu 96822.
Zhou
Q
Q
Ohta
Y
Y
Sakamoto
H
H
Hisaki
M
M
Kodama
I
I
Matsushita
T
T
Shibata
S
S
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004727:Endothelium; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010656:Phenylephrine / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000814:Aniline Compounds; D000889:Anti-Arrhythmia Agents; C092367:NC 1005; C092368:NC 1006; D011812:Quinuclidines; D010656:Phenylephrine; D011189:Potassium Chloride; D000242:Cyclic AMP; D002118:Calcium