Differential sensitivity to angiotensin II and norepinephrine in human uterine arteries

Charles R. Rosenfeld, Kevin DeSpain, R. Ann Word, Xiao Tie Liu

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Background: During pregnancy, uteroplacental responses to norepinephrine (NE) exceed systemic responses. In contrast, uteroplacental responses to angiotensin II(ANGII) are less than systemic. The explanation for these differences in uteroplacental sensitivity remain unclear but may reflect type 2 ANG II receptor (AT 2R) predominance in uterine artery (UA) vascular smooth muscle (VSM). Objective: The objective of the study was to examine VSM sensitivity to KCl, NE, and ANG II in UA from nonpregnant (NP) and pregnant (P) women and determine VSM ANG II receptor subtype expression. Methods: Responses to KCl, NE, andANGII were examined in endothelium-denudedUArings from NP (n = 28) and P (n = 13; 34-40 wk gestation) women, and ANG II receptor subtype, α 1-receptor and contractile proteins were measured. Results: KCl and NE dose dependently contracted UA (P<0.001), P exceeding NP 2-fold or greater; but α 1-receptor expressionwasunchanged.ANGII did not elicit dose effects inNPor P UA; however, P responses exceeded NP approximately 2-fold (P < 0.001) and were approximately 2.5-fold less than NE (P< 0.001). AT 2R and AT 1R expression were similar (P>0.1) in VSM from NP and term P women. AT 1R blockade abolished ANG II contractions (P < 0.001); AT 2R blockade did not enhance ANG II sensitivity in UA with or without endothelium. Actin contents increased approximately 2-fold in term UA. Conclusions: Sensitivity to α-stimulation exceeds ANG II in NP and P UA, explaining the differential uteroplacental sensitivity in pregnancy. Because AT 2R predominate in UA VSM throughout reproduction, this contributes to the inherent refractoriness to ANG II in the uterine vasculature. The increase in UA contractile proteins at term P suggests remodeling, explaining the enhanced contractility seen.

Original languageEnglish (US)
Pages (from-to)138-147
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number1
DOIs
StatePublished - Jan 1 2012

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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