Effects of sex and estrogen on chicken ductus arteriosus reactivity

Thijs W. H. Flinsenberg, Saskia van der Sterren, Anne N. H. van Cleef, M.J. Schuurman, Pia Agren, Eduardo Villamor*

*Corresponding author for this work

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Flinsenberg TWH, van der Sterren S, van Cleef ANH, Schuurman MJ, Agren P, Villamor E. Effects of sex and estrogen on chicken ductus arteriosus reactivity. Am J Physiol Regul Integr Comp Physiol 298: R1217-R1224, 2010. First published February 17, 2010; doi: 10.1152/ajpregu.00839.2009.-Sex hormones have an important influence on cardiovascular physiology and pathophysiology and sex differences in vascular reactivity have been widely demonstrated. In the present study we hypothesized 1) the presence of sexual dimorphism in chicken ductus arteriosus (DA) responsiveness to contractile and relaxant stimuli and 2) that estrogens are vasoactive in the chicken DA. In vitro contractions (assessed with a wire myograph) induced by normoxia, KCl, 4-aminopyridine, norepinephrine, phenylephrine, U46619, or endothelin-1, as well as relaxations induced by ACh, sodium nitroprusside, BAY 41-2272, PGE2, isoproterenol, forskolin, Y-27632, and hydroxyfasudil were not significantly different between males and females. The estrogen 17 beta-estradiol elicited concentration-dependent relaxation of KCl-, phenylephrine, and oxygen-induced active tone in male and female chicken DA. The stereoisomer 17 alpha-estradiol showed lesser relaxant effects, and the selective estrogen receptor (ER) agonists 4,4',4 ''-(4-propyl-[H-1]pyrazole-1,3,5-triyl)tris-phenol (ER alpha) and 2,3-bis(4-hydroxyphenyl)-propionitrile (ER alpha) did not show any effect. There were no sex differences in the responses to estrogen. Endothelium removal or the presence of the soluble guanylate cyclase inhibitor ODQ, the K+ channel blockers tetraethylammonium, glibenclamide, and charybdotoxin, or the ER antagonist fulvestrant did not modify 17 beta-estradiol-induced relaxation. CaCl2 (30 mu M-10 mM) induced concentration-dependent contraction in DA rings depolarized by 62.5 mM KCl or stimulated with 21% O-2 in Ca2+-free medium. Preincubation with 17 beta-estradiol or the L-type Ca2+ channel blocker nifedipine produced an inhibition of CaCl2-induced contractions. In conclusion, there are no sex-related differences in chicken DA reactivity. The estrogen 17 beta-estradiol induces an endothelium-independent relaxation of chicken DA that is not mediated by ER activation. This relaxant effect is, at least partially, due to inhibition of Ca2+ entry from extracellular space.
Original languageEnglish
Pages (from-to)R1217-R1224
JournalAmerican Journal of Physiology-regulatory Integrative and Comparative Physiology
Issue number5
Publication statusPublished - May 2010


  • sex differences
  • chicken embryo
  • estradiol
  • oxygen signaling

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