title: Acute gender-specific hemodynamic and inotropic effects of 17beta-estradiol on rats.
abstract: Estrogen has cardioprotective effects. In addition to beneficial effects on lipid metabolism, estrogen affects the vascular tone and may reduce endothelial dysfunction. In the present study, we examined acute gender-specific hemodynamic and inotropic effects of 17beta-estradiol (17beta-E) versus the control situation in open-chest rats. In addition to measurements in the intact circulation, myocardial function was examined on the basis of isovolumic registration independent of peripheral vascular effects. Regarding the dose-dependent and gender-specific effects of 17beta-E, in female rats, 17beta-E (50, 100, or 200 ng/kg) increased cardiac output (CO) (26%, 43%, and 59% versus control animals) as a result of reduction in total peripheral resistance (TPR) (-13%, -18%, and -24%) without any effect on myocardial contractility (isovolumic left ventricular systolic pressure, -1%, 0%, and -6%). These vascular effects are less pronounced in male rats (for 200 ng/kg 17beta-E: CO, 34%; TPR, -14%). We investigated gender-specific effects of 200 ng/kg 17beta-E after pretreatment with the estrogen receptor (ER) antagonist ICI 182,780. ER blockade reduced the effects of estrogen in female rats (CO, 29%; TPR, -17%) and male rats (CO, 19%; TPR, -11%). Regarding the effects of 200 ng/kg 17beta-E after pretreatment with N(G)-nitro-L-arginine methyl ester, NO synthesis inhibition completely prevented the acute vascular effects of estrogen in female rats (CO, -4%; TPR, 1%). In addition, immunohistochemical staining revealed no gender-specific differences of the vascular ER distribution. 17beta-E caused an acute dose-dependent and gender-specific reduction in the afterload. ERs are involved in both genders in this vasodilative effect that is mediated by NO. This NO-mediated effect may explain in part the cardioprotective effect of estrogen.
authors.affiliation: Medizinische Klinik, Abt III, Eberhard-Karls-Universität, Tübingen, Germany. martin.beyer@med.uni-tuebingen.de
authors.forename: M E
authors.initials: ME
authors.lastname: Beyer
authors.forename: G
authors.initials: G
authors.lastname: Yu
authors.forename: H
authors.initials: H
authors.lastname: Hanke
authors.forename: H M
authors.initials: HM
authors.lastname: Hoffmeister
mesh_terms: D000818:Animals; D001011:Aorta / Q000737:chemistry; D002316:Cardiotonic Agents / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000032:analysis / Q000037:antagonists & inhibitors; D012737:Sex Factors; D013268:Stimulation, Chemical
chemical_list: D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D009569:Nitric Oxide; D004958:Estradiol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester