Inhibition of cyclooxygenase but not nitric oxide synthase influences effects on the human omental artery of the thromboxane A 2 mimetic U46619 and 17β-estradiol

Yuri P. Vedernikov, Michael A. Belfort, George Saade, Robert E. Garfield

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 17β-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 rifled with Krebs buffer, 37°C, aerated with 5% carbon dioxide in air, pH approximately 7.4, for isometric tension recording. Rings were incubated with indomethacin, N ω-nitro-L-arginine, or 17β-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 ω-nitro-L-arginine changed the basal tone of omental artery rings. Neither N ω-nitro-L-arginine nor removal of the endothelium affected either the contractile action of U46619 or the relaxant action of 17β-estradiol. In contrast, indomethacin potentiated the contractile effect of U46619 and abolished the inhibitory effect of 17β-estradiol in rings from all three groups. The effects of U46619 and 17βestradiol 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 17β-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.

Original languageEnglish (US)
Pages (from-to)182-189
Number of pages8
JournalAmerican Journal of Obstetrics and Gynecology
Volume185
Issue number1
DOIs
StatePublished - 2001

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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Thromboxanes
Prostaglandin-Endoperoxide Synthases
varespladib methyl
Nitric Oxide Synthase
Estradiol
Arteries
Indomethacin
Pre-Eclampsia
Arginine
Endothelium
Pregnancy
Potassium Chloride
Eicosanoids
Carbon Dioxide
Area Under Curve
Buffers
Nitric Oxide
Air

Keywords

  • 17β-estradiol
  • Endothelium
  • Human omental artery
  • Nitric oxide
  • Preeclampsia
  • Pregnancy

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

Inhibition of cyclooxygenase but not nitric oxide synthase influences effects on the human omental artery of the thromboxane A 2 mimetic U46619 and 17β-estradiol. / Vedernikov, Yuri P.; Belfort, Michael A.; Saade, George; Garfield, Robert E.

In: American Journal of Obstetrics and Gynecology, Vol. 185, No. 1, 2001, p. 182-189.

Research output: Contribution to journalArticle

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abstract = "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 17β-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 rifled with Krebs buffer, 37°C, aerated with 5{\%} carbon dioxide in air, pH approximately 7.4, for isometric tension recording. Rings were incubated with indomethacin, N ω-nitro-L-arginine, or 17β-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 ω-nitro-L-arginine changed the basal tone of omental artery rings. Neither N ω-nitro-L-arginine nor removal of the endothelium affected either the contractile action of U46619 or the relaxant action of 17β-estradiol. In contrast, indomethacin potentiated the contractile effect of U46619 and abolished the inhibitory effect of 17β-estradiol in rings from all three groups. The effects of U46619 and 17βestradiol 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 17β-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.",
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T1 - Inhibition of cyclooxygenase but not nitric oxide synthase influences effects on the human omental artery of the thromboxane A 2 mimetic U46619 and 17β-estradiol

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AU - Belfort, Michael A.

AU - Saade, George

AU - Garfield, Robert E.

PY - 2001

Y1 - 2001

N2 - 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 17β-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 rifled with Krebs buffer, 37°C, aerated with 5% carbon dioxide in air, pH approximately 7.4, for isometric tension recording. Rings were incubated with indomethacin, N ω-nitro-L-arginine, or 17β-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 ω-nitro-L-arginine changed the basal tone of omental artery rings. Neither N ω-nitro-L-arginine nor removal of the endothelium affected either the contractile action of U46619 or the relaxant action of 17β-estradiol. In contrast, indomethacin potentiated the contractile effect of U46619 and abolished the inhibitory effect of 17β-estradiol in rings from all three groups. The effects of U46619 and 17βestradiol 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 17β-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.

AB - 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 17β-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 rifled with Krebs buffer, 37°C, aerated with 5% carbon dioxide in air, pH approximately 7.4, for isometric tension recording. Rings were incubated with indomethacin, N ω-nitro-L-arginine, or 17β-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 ω-nitro-L-arginine changed the basal tone of omental artery rings. Neither N ω-nitro-L-arginine nor removal of the endothelium affected either the contractile action of U46619 or the relaxant action of 17β-estradiol. In contrast, indomethacin potentiated the contractile effect of U46619 and abolished the inhibitory effect of 17β-estradiol in rings from all three groups. The effects of U46619 and 17βestradiol 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 17β-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.

KW - 17β-estradiol

KW - Endothelium

KW - Human omental artery

KW - Nitric oxide

KW - Preeclampsia

KW - Pregnancy

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