Effects of potassium channel blockers on the negative inotropic responses induced by cromakalim and pinacidil in guinea pig atrium

The K+ channel openers cromakalim and pinacidil induced a concentration-dependent reduction in atrial contraction force with EC50 values of 25 +/- 2 and 37 +/- 2 mumol/l, respectively. This depressant effect was antagonised by 50 mumol/l tacrine which displaced the concentration-response curves of c...

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Bibliographic Details
Published inPharmacology Vol. 45; no. 1; p. 9
Main Author Lau, W M
Format Journal Article
LanguageEnglish
Published Switzerland 1992
Subjects
Adenosine Triphosphate - metabolism
Animals
Antihypertensive Agents - pharmacology
Benzopyrans - antagonists & inhibitors
Benzopyrans - pharmacology
Cromakalim
Depression, Chemical
Female
Glyburide - pharmacology
Guanidines - antagonists & inhibitors
Guanidines - pharmacology
Guinea Pigs
Heart Atria - drug effects
Heart Atria - physiopathology
Myocardial Contraction - drug effects
Pinacidil
Potassium Channels - drug effects
Pyrroles - antagonists & inhibitors
Pyrroles - pharmacology
Stereoisomerism
Tacrine - pharmacology
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Summary:The K+ channel openers cromakalim and pinacidil induced a concentration-dependent reduction in atrial contraction force with EC50 values of 25 +/- 2 and 37 +/- 2 mumol/l, respectively. This depressant effect was antagonised by 50 mumol/l tacrine which displaced the concentration-response curves of cromakalim and pinacidil to the right. The respective DR50 values were 3.8 and 2.3. Increasing the tacrine concentration (100 and 500 mumol/l) produced no additional effect on the concentration-response relationships. Addition of 1 mumol/l atropine enhanced the antagonism due to tacrine by increasing the DR50 value from 3.8 to 6.5 for cromakalim and from 2.3 to 5.2 for pinacidil. Glibenclamide, an ATP-sensitive K+ channel blocker, competitively inhibited the negative inotropic effects of cromakalim and pinacidil. The respective dissociation constants for glibenclamide against cromakalim and pinacidil were 0.57 and 0.35 mumol/l. Neither apamin nor variation in external Ca2+ concentration affected the negative inotropic effects of the K+ channel openers. It was suggested that the mechanical effects of cromakalim and pinacidil are mediated through the ATP-sensitive K+ channels in the heart.
ISSN:0031-7012
DOI:10.1159/000138967