Differential sensitivity to angiotensin II and norepinephrine in human uterine arteries.
BACKGROUND
During pregnancy, uteroplacental responses to norepinephrine (NE) exceed systemic responses. In contrast, uteroplacental responses to angiotensin II (ANG II) are less than systemic. The explanation for these differences in uteroplacental sensitivity remain unclear but may reflect type 2 ANG II receptor (AT(2)R) 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, and ANG II were examined in endothelium-denuded UA rings 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 expression was unchanged. ANG II did not elicit dose effects in NP or 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(2)R and AT(1)R expression were similar (P > 0.1) in VSM from NP and term P women. AT(1)R blockade abolished ANG II contractions (P < 0.001); AT(2)R 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(2)R 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.
Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9063, USA. charles.rosenfeld@utsouthwestern.edu
Charles R
CR
Rosenfeld
Kevin
K
DeSpain
R Ann
RA
Word
Xiao-tie
XT
Liu
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D011247:Pregnancy; D011945:Receptors, Angiotensin / Q000378:metabolism; D055988:Uterine Artery / Q000187:drug effects*; D014599:Uterus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D011945:Receptors, Angiotensin; D000804:Angiotensin II; D009638:Norepinephrine