Vasospasmolytic effect of KRN2391 on 3,4-diaminopyridine-induced rhythmic contraction of porcine coronary artery.
1. In the present study, we examined the vasospasmolytic effect of KRN2391 on rhythmic contractions of porcine coronary artery caused by 3,4-diaminopyridine (3,4-DAP) compared with cromakalim and nitroglycerin. 2. KRN2391 at 10(-7) showed a tendency to prolong the cycle length and at 10(-6) M completely eliminated rhythmic contractions in all preparations. The elimination by 10(-6) M KRN2391 was antagonized by either oxyhemoglobin (10(-5) M) or glibenclamide (3 x 10(-6)) although not completely. 3. Cromakalim at 10(-5) M and nitroglycerin at 10(-7) M completely eliminated 3,4-DAP-induced rythmic contractions in all preparations. The elimination by cromakalim and nitroglycerin was completely antagonized by glibenclamide and oxyhemoglobin, respectively. 4. The present study suggests that the vasospasmolytic effect of KRN2391 on 3,4-DAP-induced rhythmic contractions is based on its nitrate action and K channel opening action.
Miwa
A
A
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd, Gunma, Japan.
Takeuchi
A
A
Fukata
Y
Y
Izumi
H
H
Izawa
T
T
Ogawa
N
N
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D019806:Cromakalim; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D005996:Nitroglycerin / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / 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; D015761:4-Aminopyridine; D005996:Nitroglycerin; D000077770:Amifampridine