Pharmacological analysis of the vasodepressor effect of KRN2391 in pithed rats.
1. The antagonism by glibenclamide of the vasodepressor effects of KRN2391, cromakalim and nitroglycerin was compared in pithed rats with blood pressure supported by an infusion of phenylephrine. 2. Cumulative administration of KRN2391 (3-300 micrograms/kg, i.v.), cromakalim (3-300 micrograms/kg, i.v.) and nitroglycerin (1-300 micrograms/kg, i.v.) produced dose-dependent decreases in diastolic blood pressure. 3. In rats given glibenclamide (20 mg/kg, i.v.) the dose-vasodepressor curves for KRN2391 and cromakalim were shifted to the right. However, glibenclamide had no effect on the vasodepressor effect of nitroglycerin. 4. The ED50mmHg values increased about 5.9 fold for KRN2391 and 9.5 fold for cromakalim in glibenclamide-treated rats. 5. These results suggest that the vasodepressor effect of KRN2391 is due to both glibenclamide-sensitive and insensitive mechanisms. This glibenclamide-insensitive effect of KRN2391 is thought to reflect its nitrate action.
Tanaka
Y
Y
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Yokoyama
T
T
Kashiwabara
T
T
Fukushima
H
H
Izawa
T
T
Ogawa
N
N
D000818:Animals; D001578:Benzopyrans / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D019806:Cromakalim; D003655:Decerebrate State / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; 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; D005996:Nitroglycerin; D005905:Glyburide