title: Evidence that estrogen directly and indirectly modulates C1 adrenergic bulbospinal neurons in the rostral ventrolateral medulla.
abstract: Blood pressure in women increases after menopause, and sympathetic tone in female rats decreases with estrogen injections in the rostral ventrolateral medulla (RVLM) region that contains bulbospinal C1 adrenergic neurons and is involved in blood pressure control. We investigated the anatomical and physiological basis for estrogen effects in the RVLM. Neurons with alpha- or beta-subtypes of estrogen receptor (ER) immunoreactivity (-ir) overlapped in distribution with tyrosine hydroxylase (TH)-containing C1 neurons. Immunoelectron microscopy revealed that ERalpha- and ERbeta-ir had distinct cellular and subcellular distributions. ERalpha-ir was most commonly in TH-lacking profiles, many of which were axons and peptide-containing afferents that contacted TH-containing dendrites. ERalpha-ir was also in some TH-containing dendrites. ERbeta-ir was most frequently in TH-containing somata and dendrites, particularly on endoplasmic reticula, mitochondria, and plasma membranes. In whole-cell patch clamp recordings from isolated bulbospinal RVLM neurons, 17beta-estradiol dose-dependently reduced voltage-gated Ca(++) currents, especially the long-lasting (L-type) component. This inhibition was reversed by washing or prevented by adding the non-subtype-selective ER antagonist ICI182780. An ERbeta-selective agonist, but not an ERalpha-selective agonist, reproduced the Ca(++) current inhibition. The data indicate that estrogens can modulate the function of RVLM C1 bulbospinal neurons either directly, through extranuclear ERbeta, or indirectly through extranuclear ERalpha in selected afferents. Moreover, Ca(++) current inhibition may underlie the decrease in sympathetic tone evoked by local 17beta-estradiol application. These findings provide a structural and functional basis for the effects of estrogens on blood pressure control and suggest a mechanism for the modulation of cardiovascular function by estrogen in women.
authors.affiliation: Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA. gaw2001@mail.med.cornell.edu
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Carrie T
authors.initials: CT
authors.lastname: Drake
authors.forename: Mariya
authors.initials: M
authors.lastname: Rozenblit
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Alves
authors.forename: Scott P
authors.initials: SP
authors.lastname: Herrick
authors.forename: Shinji
authors.initials: S
authors.lastname: Hayashi
authors.forename: Sudha
authors.initials: S
authors.lastname: Warrier
authors.forename: Costantino
authors.initials: C
authors.lastname: Iadecola
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Milner
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004837:Epinephrine / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D045166:Estradiol Congeners / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017698:Postmenopause / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D045166:Estradiol Congeners; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D004958:Estradiol; D014446:Tyrosine 3-Monooxygenase; D004837:Epinephrine