Differential inhibition of fetal vascular prostacyclin and platelet thromboxane synthesis by nonsteroidal anti-inflammatory drugs in humans

Prostaglandins
U M MäkiläO Ylikorkala

Abstract

To study the synthesis of proaggregatory, vasoconstricting thromboxane A2 (TxA2) by human fetal platelets we evaluated the formation of its stable metabolite thromboxane B2 (TxB2) during thrombin-induced spontaneous clotting of blood from the umbilical vein of 13 healthy infants. We further compared the effects of acetylsalicylic acid, indomethacin, naproxen sodium and diclofenac sodium on platelet TxA2 production in response to thrombin-induced aggregation during spontaneous clotting, and on prostacyclin (PGI2) production by umbilical arteries in a superfusion system by measuring the 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) concentration in the superfusate. For every drug four concentrations covering the clinically significant range were studied. The basal production of TxB2 by fetal platelets (181.5 +/- 22.5 ng/ml, mean +/- SEM) was comparable with that of adults (216.1 +/- 11.5 ng/ml). The concentrations of the drugs needed for 50% inhibition of TxB2 generation were 19.0 mumol/l for acetyl-salicylic acid, 0.09 mumol/l for indomethacin, 0.06 mumol/l for diclofenac sodium and 4.2 mumol/l for naproxen sodium. The basal production of 6-keto-PGF1 alpha by umbilical arteries was 24.5 +/- 3.2 ng/min/g. The concentrations o...Continue Reading

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Citations

Jan 1, 1990·Research in Experimental Medicine. Zeitschrift Für Die Gesamte Experimentelle Medizin Einschliesslich Experimenteller Chirurgie·K R KnightB M O'Brien
Nov 1, 1985·Prostaglandins, Leukotrienes, and Medicine·S P Hanley, J Bevan
Apr 1, 1990·The Australian and New Zealand Journal of Surgery·C G MellowB M O'Brien
Jun 1, 1995·Alcoholism, Clinical and Experimental Research·C L Randall, J L Saulnier
Oct 1, 1992·American Journal of Reproductive Immunology : AJRI·A SchoenfeldY Ovadia
Aug 1, 1986·Archives of Disease in Childhood·O YlikorkalaL Rovamo
Apr 1, 1990·Annals of Medicine·L Viinikka
Nov 1, 1988·Seminars in Arthritis and Rheumatism·R RoubenoffD B Hellmann

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