Mode of relaxing action of FK336, a new antianginal agent, in rabbit aorta.
1. FK336 (10(-6)-10(-4) M) inhibited contractile responses to norepinephrine (NE), KCl and Ca2+ in isolated rabbit aortas. 2. Relaxing effect of FK336 on KCl-response was inhibited by nitroglycerin (NG), but not by nifedipine or verapamil. 3. FK336 inhibited residual NE response and a subsequent Ca2+ response in Ca(2+)-free medium. FK336 did not affect the inositol monophosphate level. 4. Relaxing effect of FK336 on NE response was inhibited by methylene blue, NG, K(+)-channel inhibitors and acetylcholine (ACh), and potentiated by M&B 22,948 and theophylline. 8-Br cGMP and dibutyl cAMP had no effect. 5. FK336 increased cGMP level in rat aorta. 6. Potentiation of isoproterenol-relaxation by FK336 was inhibited by methylene blue. 7. The inhibitory effect of ACh on FK336-relaxation was eliminated by endothelium removal, nordihydroquaiaretic acid and guinacrine, but not by indomethacin. These treatments themselves did not affect FK336-relaxation. 8. The mode of vasorelaxing action of FK336 is discussed.
Satake
N
N
Department of Pharmacology, University of Hawaii, John A. Burns School of Medicine, Honolulu 96822.
Kiyoto
S
S
Zhou
Q
Q
Matsuo
M
M
Shibata
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D007291:Inosine Monophosphate / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011817:Rabbits; D013844:Thiazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D013844:Thiazoles; D014665:Vasodilator Agents; C076327:FK 336; D007291:Inosine Monophosphate; D011189:Potassium Chloride; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D007545:Isoproterenol; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine