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Adaptive Regulation of Endothelin Receptor Type‐A and Type‐B in Vascular Smooth Muscle Cells during Pregnancy in Rats
Author(s) -
Ou Minghui,
Dang Yiping,
Mazzuca Marc Q.,
Basile Rebecca,
Khalil Raouf A.
Publication year - 2014
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24469
Subject(s) - endocrinology , medicine , vascular smooth muscle , phenylephrine , endothelin receptor , endothelin 1 , contraction (grammar) , vasodilation , vasoconstriction , receptor , endothelium , biology , chemistry , smooth muscle , blood pressure
Normal pregnancy is associated with systemic vasodilation and decreased vascular contraction, partly due to increased release of endothelium‐derived vasodilator substances. Endothelin‐1 (ET‐1) is an endothelium‐derived vasoconstrictor acting via endothelin receptor type A (ET A R) and possibly type B (ET B R) in vascular smooth muscle cells (VSMCs), with additional vasodilator effects via endothelial ET B R. However, the role of ET‐1 receptor subtypes in the regulation of vascular function during pregnancy is unclear. We investigated whether the decreased vascular contraction during pregnancy reflects changes in the expression/activity of ET A R and ET B R. Contraction was measured in single aortic VSMCs isolated from virgin, mid‐pregnant (mid‐Preg, day 12), and late‐Preg (day 19) Sprague–Dawley rats, and the mRNA expression, protein amount, tissue and cellular distribution of ET A R and ET B R were examined using RT‐PCR, Western blots, immunohistochemistry, and immunofluorescence. Phenylephrine (Phe, 10 −5 M), KCl (51 mM), and ET‐1 (10 −6 M) caused VSMC contraction that was in late‐Preg < mid‐Preg and virgin rats. In VSMCs treated with ET B R antagonist BQ788, ET‐1 caused significant contraction that was still in late‐Preg < mid‐Preg and virgin rats. In VSMCs treated with the ET A R antagonist BQ123, ET‐1 caused a small contraction; and the ET B R agonists IRL‐1620 and sarafotoxin 6c (S6c) caused similar contraction that was in late‐Preg < mid‐Preg and virgin rats. RT‐PCR revealed similar ET A R, but greater ET B R mRNA expression in pregnant versus virgin rats. Western blots revealed similar ET A R, and greater protein amount of ET B R in endothelium‐intact vessels, but reduced ET B R in endothelium‐denuded vessels of pregnant versus virgin rats. Immunohistochemistry revealed prominent ET B R staining in the intima, but reduced ET A R and ET B R in the aortic media of pregnant rats. Immunofluorescence signal for ET A R and ET B R was less in VSMCs of pregnant versus virgin rats. The pregnancy‐associated decrease in ET A R‐ and ET B R‐mediated VSMC contraction appears to involve downregulation of ET A R and ET B R expression/activity in VSM, and may play a role in the adaptive vasodilation during pregnancy. J. Cell. Physiol. 229: 489–501, 2014. © 2013 Wiley Periodicals, Inc.