Characteristics of Ki1769, a novel vasodilator, in isolated rat aorta.
The vasorelaxant mechanism of a newly synthesized vasodilator, Ki1769 [N-cyano-N'-(2-phenethyl)-3-pyridinecarboximidamide], was studied in isolated rat aorta in comparison with cromakalim. Ki1769 (10(-8)-10(-5) M) and cromakalim (10(-8)-10(-5) M) produced a concentration-dependent relaxation and the EC50 values for Ki1769 and cromakalim were (8.60 +/- 1.90) x 10(-7) M and (1.36 +/- 0.18) x 10(-7) M, respectively. Ki1769- and cromakalim-induced relaxations were competitively antagonized by glibenclamide with pA2 values of 6.83 and 6.93, respectively. Charybdotoxin, apamine, atropine, propranolol and indomethacin did not affect the Ki1769-induced relaxation. An increase in 86Rb efflux was induced by Ki1769. Glibenclamide attenuated the increase in 86Rb efflux produced by Ki1769. These results suggest that the vasorelaxant effect of Ki1769 is based on the glibenclamide-sensitive K channel-opening action.
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
T
T
Kashiwabara
T
T
Nakajima
H
H
Kasai
S
S
Nakajima
T
T
Izawa
N
N
Ogawa
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012414:Rubidium Radioisotopes; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001578:Benzopyrans; D015221:Potassium Channels; D011725:Pyridines; D011758:Pyrroles; D012414:Rubidium Radioisotopes; D014665:Vasodilator Agents; D019806:Cromakalim; C084622:Ki 1769; D005905:Glyburide