title: Effects of sex and estrogen on chicken ductus arteriosus reactivity.
abstract: 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, PGE(2), 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 4,4',4''-(4-propyl-[(1)H]pyrazole-1,3,5-triyl)tris-phenol (ERalpha) and 2,3-bis(4-hydroxyphenyl)-propionitrile (ERbeta) 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 17beta-estradiol-induced relaxation. CaCl(2) (30 muM-10 mM) induced concentration-dependent contraction in DA rings depolarized by 62.5 mM KCl or stimulated with 21% O(2) in Ca(2+)-free medium. Preincubation with 17beta-estradiol or the L-type Ca(2+) channel blocker nifedipine produced an inhibition of CaCl(2)-induced contractions. In conclusion, there are no sex-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.
authors.affiliation: Department of Pediatrics, Maastricht University Medical Center, GROW School for Oncology and Developmental Biology, P. Debyelaan 25, Maastricht, The Netherlands.
authors.forename: Thijs W H
authors.initials: TW
authors.lastname: Flinsenberg
authors.forename: Saskia
authors.initials: S
authors.lastname: van der Sterren
authors.forename: Anne N H
authors.initials: AN
authors.lastname: van Cleef
authors.forename: Marijn J
authors.initials: MJ
authors.lastname: Schuurman
authors.forename: Pia
authors.initials: P
authors.lastname: Agren
authors.forename: Eduardo
authors.initials: E
authors.lastname: Villamor
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000109:Acetylcholine; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002642:Chick Embryo; D002645:Chickens; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004373:Ductus Arteriosus / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000819:agonists; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D026902:Potassium Channel Blockers; D011720:Pyrazoles; D011725:Pyridines; D011960:Receptors, Estrogen; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D005576:Colforsin; D004958:Estradiol; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015761:4-Aminopyridine; D015232:Dinoprostone; D000109:Acetylcholine; D010100:Oxygen; D002118:Calcium; D009638:Norepinephrine