Premium
Differences between the effects of cromakalim and nifedipine on agonist‐induced responses in rabbit aorta
Author(s) -
Bray K.M.,
Weston A.H.,
Duty S.,
Newgreen D.T.,
Longmore J.,
Edwards G.,
Brown T.J.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12175.x
Subject(s) - cromakalim , nifedipine , chemistry , glibenclamide , pharmacology , muscle contraction , hyperpolarization (physics) , contraction (grammar) , medicine , agonist , calcium , anesthesia , endocrinology , biochemistry , stereochemistry , receptor , organic chemistry , nuclear magnetic resonance spectroscopy , diabetes mellitus
1 The effects of cromakalim on endothelium‐denuded rabbit aortic strips were compared with those of the calcium (Ca 2+ ) entry blocking agent, nifedipine. 2 Pre‐incubation with cromakalim or nifedipine had no significant effect on the initial phasic component of noradrenaline (NA)‐induced responses. 3 Cromakalim (0.3–10 μ m ), but not nifedipine, inhibited the maintained tonic contractions produced by NA. The effects of cromakalim were antagonized by raising extracellular [K + ] or by glibenclamide. 4 Nifedipine inhibited contractions produced by KCl (40 m m ) whereas cromakalim had no effect. 5 In Ca 2+ ‐free physiological salt solution (PSS), cromakalim produced a significant inhibition of both the refilling of and the release of Ca 2+ from NA‐releasable Ca 2+ stores, whereas nifedipine was ineffective. 6 In tissues preloaded with 42 K + cromakalim (0.3–10 μ m ) produced a concentration‐dependent increase in the 42 K + efflux rate coefficient. NA (0.3 μ m ) also produced an increase in the rate of efflux of 42 K + , an effect which was not antagonized by nifedipine (0.3 μ m ). 7 When microelectrodes were used, cromakalim (1–10 μ m ) produced a maintained concentration‐dependent membrane hyperpolarization. However, low concentrations of cromakalim (<1 μ m ) which relaxed the aorta had no effect on membrane potential. NA had no significant effect on membrane potential. 9 It is concluded that the ability of cromakalim to relax NA‐induced contractions in rabbit aorta is not exerted by the indirect closure of nifedipine‐sensitive Ca 2+ channels. Instead, cromakalim may exert a direct inhibitory action on Ca 2+ uptake into and release from Ca 2+ stores and additionally inhibit the pathway through which Ca 2+ passes from the extracellular fluid to intracellular Ca 2+ stores.