Endothelin-induced contractions in human placental blood vessels are enhanced in intrauterine growth retardation, and modulated by agents that regulate levels of intracellular calcium.
Endothelin-1 (ET-1) is a strongly vasoactive polypeptide that may be involved in the regulation of the uteroplacental blood flow. In the present study we have examined the contractile response to ET-1 in human placental arteries in the presence of several agents that interfere with storage of intracellular calcium, e.g. caffeine, ryanodine and thapsigargin. We have also compared the contractile response to ET-1 in normal pregnancies with that of patients with foetal intrauterine growth retardation (IUGR), a condition with reduced uteroplacental blood flow. We found that the response to ET-1 in the placental arteries from women with normal pregnancies was reduced by 20% in the absence of extracellular calcium. Caffeine relaxed the basal tone of the vessels and reduced the contractile response to ET-1 by 51%. Nifedipine in addition to caffeine resulted in a reduction of 70%. Ryanodine also reduced the tone. Thapsigargin had no effect on the placental arteries at lower concentrations, but gave a progressive and slow contraction at 10(-6) M. The ET-1 induced contraction in placental arteries from IUGR patients was 67% more potent than in placental arteries from women with normal pregnancies, 129% as compared with 77% of the maximal K(+)-induced contraction. We conclude that the ET-1-induced contractile response in the human placental artery is dependent on influx of extracellular calcium as well as mobilization of calcium from intracellular stores. An increased sensitivity to ET-1 in placental arteries may contribute to the reduced uteroplacental blood flow in intrauterine growth retardation.
Liu
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YA
Department of Women and Child Health, Karolinska Institute and Hospital, Stockholm, Sweden.
Ostlund
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E
Fried
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G
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000328:Adult; D001158:Arteries / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D016232:Endothelins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D021041:Placental Circulation / Q000502:physiology; D011247:Pregnancy; D012433:Ryanodine / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D016232:Endothelins; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D013729:Terpenes; D012433:Ryanodine; D002110:Caffeine; D019284:Thapsigargin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D002118:Calcium