Inhibition of cyclooxygenase but not nitric oxide synthase influences effects on the human omental artery of the thromboxane A2 mimetic U46619 and 17beta-estradiol

Am J Obstet Gynecol. 2001 Jul;185(1):182-9. doi: 10.1067/mob.2001.113909.


Objective: These experiments were performed to study the influence of endothelial factors on the contractile effect of the thromboxane A(2) analog U46619 and on the relaxant action of 17beta-estradiol on isolated human omental arteries from nonpregnant women, women with normal pregnancies, and women with preeclampsia.

Study design: Arterial rings (3 mm) with or without endothelium were suspended in organ chambers filled with Krebs buffer, 37 degrees C, aerated with 5% carbon dioxide in air, pH approximately 7.4, for isometric tension recording. Rings were incubated with indomethacin, N(omega)-nitro-L -arginine, or 17beta-estradiol, alone or in combination. The concentration that produced 50% of maximal effect, the area under the curve, and the maximal effect of U46619, normalized with respect to a reference contraction in response to potassium chloride, were compared.

Results: Neither indomethacin nor N(omega)-nitro-L -arginine changed the basal tone of omental artery rings. Neither N(omega)-nitro-L -arginine nor removal of the endothelium affected either the contractile action of U46619 or the relaxant action of 17beta-estradiol. In contrast, indomethacin potentiated the contractile effect of U46619 and abolished the inhibitory effect of 17beta-estradiol in rings from all three groups. The effects of U46619 and 17beta-estradiol were significantly less in rings from women with normal pregnancy than in those from women with preeclampsia. Tissues from women with preeclampsia demonstrated the highest contractile response to U46619.

Conclusion: The inhibitory effect of 17beta-estradiol is not due to increased production of endothelial nitric oxide but rather involves inhibitory products of the cyclooxygenase pathway. The effect of indomethacin may result from inhibited production or release of eicosanoids or from sensitization of thromboxane A(2) receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology*
  • Adult
  • Arteries / drug effects*
  • Arteries / physiology
  • Cyclooxygenase Inhibitors / pharmacology*
  • Drug Synergism
  • Endothelium, Vascular / physiology
  • Enzyme Inhibitors / pharmacology
  • Estradiol / pharmacology*
  • Female
  • Humans
  • Indomethacin / pharmacology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Omentum / blood supply*
  • Organ Culture Techniques
  • Pre-Eclampsia / physiopathology
  • Pregnancy
  • Vasoconstrictor Agents / pharmacology
  • Vasodilator Agents / pharmacology


  • Cyclooxygenase Inhibitors
  • Enzyme Inhibitors
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Estradiol
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester
  • Indomethacin