Comparison of the anti-vasoconstrictor effects of a novel vasodilator KRN2391, nicorandil and nifedipine on isolated porcine large coronary artery.
The anti-vasoconstrictor profile of KRN2391, a novel vasodilator, was compared with that of nicorandil and nifedipine in isolated porcine large coronary arteries contracted by KCl, noradrenaline, serotonin, acetylcholine, endothelin-1 and U46619, a thromboxane A2 analogue. KRN2391 (10(-8) - 3 x 10(-5) M), nicorandil (10(-7) - 3 x 10(-4) M) and nifedipine (10(-10) - 10(-5) M) inhibited these contractile responses in a concentration-dependent manner. KRN2391 and nicorandil completely abolished these contractile responses at their maximum effects. However, nifedipine caused less inhibition than KRN2391 and nicorandil and did not completely abolish the contractile responses. The relaxant activity of KRN2391 was more potent than that of nicorandil. This study shows that the anti-vasoconstrictor profiles of KRN2391, nicorandil and nifedipine involve different relaxant mechanisms.
Kasai
H
H
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Jinno
Y
Y
Kaneta
S
S
Tanaka
Y
Y
Fukushima
H
H
Izawa
T
T
Ogawa
N
N
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D016232:Endothelins; D011450:Prostaglandin Endoperoxides, Synthetic; D011725:Pyridines; D014665:Vasodilator Agents; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; D009536:Niacinamide; D020108:Nicorandil; D012701:Serotonin; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009543:Nifedipine; D000109:Acetylcholine; D009638:Norepinephrine