Pregnancy reduces RhoA/Rho kinase and protein kinase C signaling pathways downstream of thromboxane receptor activation in the rat uterine artery

Styliani Goulopoulou, Johanna L. Hannan, Takayuki Matsumoto, R Clinton Webb

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

During pregnancy, reduced vascular responses to constrictors contribute to decreased uterine and total vascular resistance. Thromboxane A2 (TxA2) is a potent vasoconstrictor that exerts its actions via diverse signaling pathways, and its biosynthesis increases in preeclampsia. In this study, we hypothesized that maternal vascular responses to TxA2 will be attenuated via Rho kinase, PKC, p38 MAPK, and ERK1/2 signaling pathways. Isolated ring segments of uterine and small mesenteric arteries from late pregnant (19-21 days) and virgin rats were suspended in a myograph, and isometric force was measured. Pregnancy did not affect uterine and mesenteric artery responses to the TxA2 analog U-46619 (10-9-10-5 M), but transduction signals associated with these contractions were different between pregnant and nonpregnant rats. Inhibition of Rho kinase (10-6 M Y-27632) reduced sensitivity to U-46619 in virgin uterine vessels but did not inhibit these contractions in pregnant uterine arteries and had no effect on mesenteric vessels. Treatment of arterial segments with a PKC inhibitor (10-6 M bisindolylmaleimide I) reduced U-46619-induced contractions in virgin uterine and mesenteric arteries and in pregnant mesenteric arteries. Pregnant uterine arteries, however, were unresponsive to PKC inhibition. Inhibition of ERK1/2 (10-5 M PD-98059) and p38 MAPK (10-5 M SB-203580) reduced U46619-induced contractions in nonpregnant vessels and in pregnant uterine and mesenteric vessels. These data suggest that normal pregnancy does not affect uterine and mesenteric contractile responses to TxA2 but reduces the contribution of Rho kinase and PKC signaling pathways to these contractions in the uterine vasculature. In contrast, the role of ERK1/2 and p38 MAPK in U-46619-induced uterine contractions remains unchanged with pregnancy. TxA2-associated transduction signals and its regulators might present potential targets for the development of new treatments for preeclampsia and other pregnancy-associated vascular diseases.

Original languageEnglish (US)
Pages (from-to)2477-2488
Number of pages12
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume302
Issue number12
DOIs
StatePublished - Jun 15 2012

Fingerprint

Thromboxane Receptors
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Uterine Artery
rho-Associated Kinases
Thromboxane A2
Mesenteric Arteries
Protein Kinase C
p38 Mitogen-Activated Protein Kinases
Pregnancy
Uterine Contraction
Pre-Eclampsia
Blood Vessels
Signal Transduction
MAP Kinase Signaling System
Vasoconstrictor Agents
Vascular Diseases
Vascular Resistance
Mothers

Keywords

  • Gestation
  • Prostanoid receptor
  • Prostanoids
  • Thromboxane A
  • Vascular reactivity

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Pregnancy reduces RhoA/Rho kinase and protein kinase C signaling pathways downstream of thromboxane receptor activation in the rat uterine artery. / Goulopoulou, Styliani; Hannan, Johanna L.; Matsumoto, Takayuki; Webb, R Clinton.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 302, No. 12, 15.06.2012, p. 2477-2488.

Research output: Contribution to journalArticle

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