Differences between the effects of cromakalim and nifedipine on agonist-induced responses in rabbit aorta
| Autor: | Gillian Edwards, K.M. Bray, T.J. Brown, D. T. Newgreen, Arthur H. Weston, J. Longmore, Susan Duty |
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| Rok vydání: | 1991 |
| Předmět: |
Male
Cromakalim Nifedipine chemistry.chemical_element Aorta Thoracic Vasodilation In Vitro Techniques Pharmacology Calcium Membrane Potentials Glibenclamide Norepinephrine chemistry.chemical_compound Extracellular fluid medicine Animals Benzopyrans Pyrroles Membrane potential musculoskeletal neural and ocular physiology Membrane hyperpolarization musculoskeletal system chemistry Anesthesia Potassium cardiovascular system Rabbits Research Article circulatory and respiratory physiology medicine.drug |
| Zdroj: | British Journal of Pharmacology. 102:337-344 |
| ISSN: | 0007-1188 |
| DOI: | 10.1111/j.1476-5381.1991.tb12175.x |
| Popis: | 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 microM), 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 microM) produced a concentration-dependent increase in the 42K+ efflux rate coefficient. NA (0.3 microM) also produced an increase in the rate of efflux of 42K+, an effect which was not antagonized by nifedipine (0.3 microM). 7. When microelectrodes were used, cromakalim (1-10 microM) produced a maintained concentration-dependent membrane hyperpolarization. However, low concentrations of cromakalim (less than 1 microM) 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 Ca2+ 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. |
| Databáze: | OpenAIRE |
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