Pharmacological analysis of the effect of KRN2391 on coronary vasculature in perfused rat heart.
1. The antagonism by glibenclamide of the effects of KRN2391, cromakalim and nifedipine on coronary flow (CF) were compared in isolated perfused rat hearts. 2. KRN2391, cromakalim and nifedipine increased CF in a concentration-dependent manner. In the presence of glibenclamide, the concentration-effect curves on CF for KRN2391 and cromakalim shifted to the right but that for nifedipine did not change. 3. The EC50 values increased about 6.6-fold for KRN2391 and 19.0-fold for cromakalim in the presence of glibenclamide. 4. These results suggest that the increase in CF induced by KRN2391 is due to both glibenclamide-sensitive and insensitive mechanisms.
Miwa
A
A
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd., Gunma, Japan.
Jinno
Y
Y
Yokoyama
T
T
Izawa
T
T
Ogawa
N
N
D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010477:Perfusion; D015221:Potassium Channels / Q000187:drug effects*; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011758:Pyrroles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001578:Benzopyrans; D015221:Potassium Channels; D011725:Pyridines; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; C070492:N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide methanesulfonate; D009543:Nifedipine; D005905:Glyburide