Effects of Ca2+ antagonists nifedipine and diltiazem on isolated human chorionic arteries and veins.
5-Hydroxytryptamine (5-HT) and K+ induced contractions in human chorionic arteries and veins. 5-HT-caused responses were blocked by ketanserin (10(-7) and 10(-6) M) and prazosin (10(-5) but not 10(-6) M). K(+)-induced contractions were practically abolished in a Ca2(+)-free medium, whereas those produced by 5-HT were reduced. The efficacy (EC50 values) of diltiazem to produce relaxation in arteries and veins contracted with 40 or 75 mM K+ was similar, but normally greater than that of nifedipine. The potency of nifedipine (IC50 values) to inhibit maximal K+ contractions was greater than to inhibit maximal 5-HT contractions; diltiazem showed an inverse order of potency, which was less than that of nifedipine. The time course of 10(-6) M 5-HT and 75 mM K+ contractions was different, as much in the absence as in the presence of both Ca2+ antagonists; 5-HT contractions were transient, but sustained those elicited by K+. K+ (75 mM) and 5-HT (10(-6) M) produced increases in 45Ca2+ uptake, which were reduced by the Ca2+ antagonists. These results indicate that (a) human chorionic arteries and veins are similarly sensitive to Ca2+ antagonists, (b) 5-HT-induced contractions were largely dependent on extracellular Ca2+ and mainly mediated by 5-HT2 receptors but not by alpha 1-adrenoceptors, and (c) nifedipine was more potent than diltiazem in inhibiting Ca2+ influx through potential- and receptor-dependent Ca2+ channels.
Reviriego
J
J
Departamento de Farmcología y Terapéutica, Facultad de Medicina, Universidad de Extremadura, Madrid, Spain.
Fernandez-Alfonso
M S
MS
Guerra
P
P
Marín
J
J
D001158:Arteries / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D010920:Placenta / Q000098:blood supply; D011188:Potassium / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011247:Pregnancy; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D014680:Veins / Q000187:drug effects
D002132:Calcium Radioisotopes; D012701:Serotonin; D007650:Ketanserin; D004110:Diltiazem; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D011224:Prazosin