Differences between the effects of cromakalim and nifedipine on agonist‐induced responses in rabbit aorta

Abstract

1 The effects of cromakalim on endothelium‐denuded rabbit aortic strips were compared with those of the calcium (Ca²⁺) 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 μm), 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 mm) whereas cromakalim had no effect. 5 In Ca²⁺‐free physiological salt solution (PSS), cromakalim produced a significant inhibition of both the refilling of and the release of Ca²⁺ from NA‐releasable Ca²⁺ stores, whereas nifedipine was ineffective. 6 In tissues preloaded with ⁴²K⁺ cromakalim (0.3–10 μm) produced a concentration‐dependent increase in the ⁴²K⁺ efflux rate coefficient. NA (0.3 μm) also produced an increase in the rate of efflux of ⁴²K⁺, an effect which was not antagonized by nifedipine (0.3 μm). 7 When microelectrodes were used, cromakalim (1–10 μm) produced a maintained concentration‐dependent membrane hyperpolarization. However, low concentrations of cromakalim (2+ channels. Instead, cromakalim may exert a direct inhibitory action on Ca²⁺ uptake into and release from Ca²⁺ stores and additionally inhibit the pathway through which Ca²⁺ passes from the extracellular fluid to intracellular Ca²⁺ stores.