Characteristics of KRN2391, a novel vasodilator, compared with those of cromakalim, pinacidil and nifedipine in rat aorta.
The characteristics of KRN2391, a novel vasodilator, were studied in rat isolated aorta. The effects of KRN2391, cromakalim, pinacidil and nifedipine on the contractions induced by 20, 40 and 80 mM K+ and by 10(-7) M norepinephrine (NE) were measured first. KRN2391, cromakalim and pinacidil selectively inhibited the contractions induced by 20 mM K+ and NE rather than those induced by high concentrations of K+. Nifedipine could not completely inhibit the NE-induced contractions. The vasorelaxant effect of KRN2391 was inhibited by K+ channel blockers and guanylate cyclase inhibitors. KRN2391, cromakalim and pinacidil increased the 86Rb efflux rate coefficient. Thus, KRN2391 exhibits a vasodilator profile similar to that of the K+ channel openers and induces an increase in 86Rb efflux. It is suggested that opening of the membrane K+ channels may be partly involved in the vasorelaxant mechanism of KRN2391.
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
T
T
Kashiwabara
S
S
Nakajima
T
T
Izawa
H
H
Fukushima
K
K
Nishikori
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology*; D009585:Nitrogen Dioxide / Q000494:pharmacology; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D006146:Guanidines; D015221:Potassium Channels; D011725:Pyridines; D011758:Pyrroles; D012414:Rubidium Radioisotopes; D014665:Vasodilator Agents; D019806:Cromakalim; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; D020110:Pinacidil; D006162:Guanylate Cyclase; D009543:Nifedipine; D009585:Nitrogen Dioxide