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RESEARCH PRODUCT

Effects of Ca2+ entry blockers on CaCl2-, KCl- and noradrenaline-induced contractions of goat cerebral arteries

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Abstract The effects of three Ca 2+ entry blockers, nicardipine, nimodipine and verapamil, on CaCl 2 -, KCl- and noradrenaline-induced contractions were examined in isolated goat middle cerebral artery. The relationship between the effects of Ca 2+ entry blockers and the extracellular Ca 2+ dependence of the contractions was also examined. In ‘nominally’ Ca 2+ -free medium, addition of CaCl 2 induced concentration-dependent contractions of previously depolarized arteries. Withdrawal of Ca 2+ from the extracellular medium caused strong inhibition of the KCl- and noradrenaline-induced arterial contractions. Addition of EGTA to the Ca 2+ -free medium almost abolished the noradrenaline-response but did not increase the inhibition of the KCl-induced contractions. The Ca 2+ entry blockers induced concentration-dependent relaxation of the precontracted arteries (100 mM KCl) with the following order of potency: nimodipine > nicardipine > verapamil. The CaCl 2 -, KCl- and noradrenaline-induced contractions were depressed in a concentration-related manner by nicardipine, nimodipine and verapamil. Dihydropyridines showed a greater inhibitory effect than verapamil. These results show that Ca 2+ entry blockers are able to inhibit the contractile responses of goat cerebral arteries to KCl and noradrenaline, an effect which may be explained by the strong dependence of both responses on extracellular Ca 2+ .