Effects of Ca2+ entry blockers on CaCl2-, KCl- and noradrenaline-induced contractions of goat cerebral arteries.
The effects of three Ca2+ entry blockers, nicardipine, nimodipine and verapamil, on CaCl2-, KCl- and noradrenaline-induced contractions were examined in isolated goat middle cerebral artery. The relationship between the effects of Ca2+ entry blockers and the extracellular Ca2+ dependence of the contractions was also examined. In 'nominally' Ca2(+)-free medium, addition of CaCl2 induced concentration-dependent contractions of previously depolarized arteries. Withdrawal of Ca2+ from the extracellular medium caused strong inhibition of the KCl- and noradrenaline-induced arterial contractions. Addition of EGTA to the Ca2(+)-free medium almost abolished the noradrenaline-response but did not increase the inhibition of the KCl-induced contractions. The Ca2+ entry blockers induced concentration-dependent relaxation of the precontracted arteries (100 mM KC1) with the following order of potency: nimodipine greater than nicardipine greater than verapamil. The CaCl2-, 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 Ca2+ 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 Ca2+.
Salom
J B
JB
Centro de Investigación, Hospital La Fe, Valencia, Spain.
Torregrosa
G
G
Miranda
F J
FJ
Alabadí
J A
JA
Alvarez
C
C
Alborch
E
E
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D006041:Goats; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004533:Egtazic Acid; D009553:Nimodipine; D011189:Potassium Chloride; D014700:Verapamil; D009529:Nicardipine; D002122:Calcium Chloride; D009638:Norepinephrine