Potassium channel opening properties of a novel compound, NIP-121, cromakalim and nicorandil in rat aorta and portal vein.
A novel compound, NIP-121, cromakalim and nicorandil caused concentration-dependent relaxation of rat aortas precontracted with 30 mM KCl, with pEC50 (M) values of 8.2, 7.1 and 5.5, respectively. At 60 mM KCl, the vasorelaxation induced by NIP-121 or cromakalim was almost abolished whereas that induced by nicorandil remained. In preparations precontracted with prostaglandin F2 alpha(PGF2 alpha) (10(-5) M), glibenclamide (10(-7) M) and phentolamine (3 x 10(-6), 3 x 10(-5) M) antagonized the relaxation induced by NIP-121 and cromakalim but not that induced by nicorandil. Methylene blue (10(-5) M) showed antagonistic effects against the vasorelaxation induced by nicorandil but not that induced by NIP-121. NIP-121 (10(-7), 10(-6) M) and cromakalim (10(-6), 10(-5) M) significantly increased the 86Rb+ efflux rate in rat aorta. The three compounds inhibited the frequency of spontaneous contractions of the rat portal vein (pIC30; NIP-121 = 8.0, cromakalim = 7.1 and nicorandil = 4.9); glibenclamide and phentolamine antagonized the effects of these compounds. In conclusion, NIP-121 is a more potent K+ channel opener than cromakalim in these tissues. Nicorandil apparently behaves as a K+ channel opener in the rat portal vein, but the vasorelaxation may involve some other mechanisms, such as generation of cyclic GMP.
Masuda
Y
Y
Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd., Saitama, Japan.
Arakawa
C
C
Yamashita
T
T
Miyajima
M
M
Shigenobu
K
K
Kasuya
Y
Y
Tanaka
S
S
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D010069:Oxadiazoles / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011169:Portal Vein / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes
D000959:Antihypertensive Agents; D001578:Benzopyrans; D010069:Oxadiazoles; D010880:Piperidines; D015221:Potassium Channels; D011758:Pyrroles; D012414:Rubidium Radioisotopes; D019806:Cromakalim; D009536:Niacinamide; D020108:Nicorandil; D011189:Potassium Chloride; C070366:NIP 121; D005905:Glyburide; D010646:Phentolamine