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Flinsenberg TW, Van der Sterren S, van Cleef AN, Schuurman MJ, Agren P, Villamor E: Effects of gender and estrogen on chicken ductus arteriosus reactivity. Am J Physiol Regul Integr Comp Physiol. 2010 Feb 17.
Sex hormones have an important influence on cardiovascular physiology and pathophysiology and gender differences in vascular reactivity have been widely demonstrated. In the present study we hypothesized 1) the presence of sexual dimorphism in chicken 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 acetylcholine, sodium nitroprusside, BAY 41-2272, prostaglandin E2, isoproterenol, forskolin,Y-27632, and hydroxyfasudil were not significantly different between males and females. The estrogen 17beta-estradiol elicited concentration-dependent relaxation of KCl-, phenylephrine-, and oxygen-induced active tone in male and female chicken DA. The stereoisomer 17alpha-estradiol showed lesser relaxant effects and the selective estrogen receptor (ER) agonists PPT (ERalpha) and DPN (ERbeta) did not show any effect. There were no gender 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 charydobtoxin, or the ER antagonist fulvestrant did not modify 17beta-estradiol-induced relaxation. CaCl2 (30 muM -10 mM) induced concentration-dependent contraction in DA rings depolarized by 62.5 mM KCl or stimulated with 21% O2 in Ca (2+)-free medium. Preincubation with 17beta-estradiol or the L-type Ca (2+) channel blocker nifedipine produced an inhibition of CaCl2-induced contractions. In conclusion, there are no gender-related differences in chicken DA reactivity. The estrogen 17beta-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 Ca (2+) entry from extracellular space. Key words: ductus arteriosus, estrogen, chicken, embryo. |
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