Comparison of the anticonstrictor action of dihydropyridines (nimodipine and nicardipine) and Mg2+ in isolated human cerebral arteries.
The isometric tension recorded from ring segments of branches of human middle cerebral artery was the parameter used to study the inhibition of spasmogen-induced contractions as model for cerebral vasospasm. Concentration-response curves to 5-hydroxytryptamine (10(-9)-3 x 10(-5) M) and prostaglandin F2 alpha (10(-7)-3 x 10(-5) M) were inhibited in Ca(2+)-free medium and in Ca(2+)-free medium to which EGTA (1 mM) had been added, respectively. Nimodipine (10(-7), 10(-5) M), nicardipine (10(-7), 10(-5) M) and Mg2+ (magnesium sulfate 10(-4), 10(-2) M) inhibited the 5-HT-elicited contractions, and this inhibition was similar for the highest concentrations tested. In contrast, nimodipine and nicardipine were more effective than Mg2+ to inhibit the prostaglandin F2 alpha-elicited contractions. Nimodipine (10(-9)-10(-5) M), nicardipine (10(-9)-10(-5) M) and Mg2+ (10(-5)-3 x 10(-2) M) relaxed the arteries precontracted with PGF2 alpha (10(-5) M), but nicardipine was the most potent relaxant drug. Because 5-hydroxytryptamine and prostaglandin F2 alpha may be involved in the pathogenesis of cerebral vasospasm, nimodipine, nicardipine, and Mg2+ could be used in the pharmacological treatment of this disorder. However, dihydropyridines (particularly nicardipine) are more potent anticonstrictors than Mg2+.
Alborch
E
E
Centro de Investigación, Hospital Universitario La Fe, Valencia, Spain.
Salom
J B
JB
Perales
A J
AJ
Torregrosa
G
G
Miranda
F J
FJ
Alabadí
J A
JA
Jover
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000517:prevention & control; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009529:Nicardipine / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D012701:Serotonin; D009553:Nimodipine; D015237:Dinoprost; D009529:Nicardipine; D008274:Magnesium; D002118:Calcium