Dissimilarity in the mechanisms of action of KRN2391, nicorandil and cromakalim in canine renal artery.
In the present study, we examined the mode of action of KRN2391 (N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulphonate) in isolated canine renal artery compared with those of nicorandil and cromakalim. KRN2391 (10(-8)-3 x 10(-5) M), nicorandil (10(-7)-3 x 10(-4) M) and cromakalim (10(-8)-3 x 10(-5) M) relaxed renal arteries contracted by 25 mM KCl in a concentration-dependent manner. KRN2391-induced relaxation was inhibited by methylene blue (10(-5) M) and glibenclamide (10(-6) M). Nicorandil-induced relaxation was inhibited by methylene blue, but not by glibenclamide. The concentration-relaxation curve for cromakalim displayed a rightward parallel shift in the presence of glibenclamide. In the control observation, KRN2391 and nicorandil also produced full relaxation, but cromakalim did not. The present results suggest that KRN2391 acts as both a nitrate and a potassium channel opener, and nicorandil acts only as a nitrate and only in canine renal artery.
Kasai
H
H
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd., Gunma, Japan.
Fukata
Y
Y
Harada
K
K
Fukushima
H
H
Ogawa
N
N
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D009566:Nitrates / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D012077:Renal Artery / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D009566:Nitrates; D015221:Potassium Channels; D011725:Pyridines; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; D009536:Niacinamide; D020108:Nicorandil; D011189:Potassium Chloride; D005905:Glyburide; D008751:Methylene Blue