title: Estrogen receptor-alpha mediates estrogen facilitation of baroreflex heart rate responses in conscious mice.
abstract: Estrogen facilitates baroreflex heart rate responses evoked by intravenous infusion of ANG II and phenylephrine (PE) in ovariectomized female mice. The present study aims to identify the estrogen receptor subtype involved in mediating these effects of estrogen. Baroreflex responses to PE, ANG II, and sodium nitroprusside (SNP) were tested in intact and ovariectomized estrogen receptor-alpha knockout (ERalphaKO) with (OvxE+) or without (OvxE-) estrogen replacement. Wild-type (WT) females homozygous for the ERalpha(+/+) were used as controls. Basal mean arterial pressures (MAP) and heart rates were comparable in all the groups except the ERalphaKO-OvxE+ mice. This group had significantly smaller resting MAP, suggesting an effect of estrogen on resting vascular tone possibly mediated by the ERbeta subtype. Unlike the WT females, estrogen did not facilitate baroreflex heart rate responses to either PE or ANG II in the ERalphaKO-OvxE+ mice. The slope of the line relating baroreflex heart rate decreases with increases in MAP evoked by PE was comparable in ERalphaKO-OvxE- (-6.97 +/- 1.4 beats.min(-1).mmHg(-1)) and ERalphaKO-OvxE+ (-6.18 +/- 1.3) mice. Likewise, the slope of the baroreflex bradycardic responses to ANG II was similar in ERalphaKO-OvxE- (-3.87 +/- 0.5) and ERalphaKO-OvxE+(-2.60 +/- 0.5) females. Data suggest that estrogen facilitation of baroreflex responses to PE and ANG II is predominantly mediated by ERalpha subtype. A second important observation in the present study is that the slope of ANG II-induced baroreflex bradycardia is significantly blunted compared with PE in the intact as well as the ERalphaKO-OvxE+ females. We have previously reported that this ANG II-mediated blunting of cardiac baroreflexes is observed only in WT males and not in ovariectomized WT females independent of their estrogen replacement status. The present data suggest that in females lacking ERalpha, ANG II causes blunting of cardiac baroreflexes similar to males and may be indicative of a direct modulatory effect of the ERalpha on those central mechanisms involved in ANG II-induced resetting of cardiac baroreflexes. These observations suggest an important role for ERalpha subtype in the central modulation of baroreflex responses. Lastly, estrogen did not significantly affect reflex tachycardic responses to SNP in both WT and ERalphaKO mice.
authors.affiliation: Dalton Cardiovascular Research Center, University of Missouri, Columbia 65211, USA. PamidimukkalaJ@missouri.edu <PamidimukkalaJ@missouri.edu>
authors.forename: Jaya
authors.initials: J
authors.lastname: Pamidimukkala
authors.forename: Baojian
authors.initials: B
authors.lastname: Xue
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Newton
authors.forename: Dennis B
authors.initials: DB
authors.lastname: Lubahn
authors.forename: Meredith
authors.initials: M
authors.lastname: Hay
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003243:Consciousness; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009599:Nitroprusside / Q000494:pharmacology; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D009599:Nitroprusside; D010656:Phenylephrine