title: Roles for the sympathetic nervous system, renal nerves, and CNS melanocortin-4 receptor in the elevated blood pressure in hyperandrogenemic female rats.
abstract: Women with polycystic ovary syndrome (PCOS) have hyperandrogenemia and increased prevalence of risk factors for cardiovascular disease, including elevated blood pressure. We recently characterized a hyperandrogenemic female rat (HAF) model of PCOS [chronic dihydrotestosterone (DHT) beginning at 4 wk of age] that exhibits similar characteristics as women with PCOS. In the present studies we tested the hypotheses that the elevated blood pressure in HAF rats is mediated in part by sympathetic activation, renal nerves, and melanocortin-4 receptor (MC4R) activation. Adrenergic blockade with terazosin and propranolol or renal denervation reduced mean arterial pressure (MAP by telemetry) in HAF rats but not controls. Hypothalamic MC4R expression was higher in HAF rats than controls, and central nervous system MC4R antagonism with SHU-9119 (1 nmol/h icv) reduced MAP in HAF rats. Taking a genetic approach, MC4R null and wild-type (WT) female rats were treated with DHT or placebo from 5 to 16 wk of age. MC4R null rats were obese and had higher MAP than WT control rats, and while DHT increased MAP in WT controls, DHT failed to further increase MAP in MC4R null rats. These data suggest that increases in MAP with chronic hyperandrogenemia in female rats are due, in part, to activation of the sympathetic nervous system, renal nerves, and MC4R and may provide novel insights into the mechanisms responsible for hypertension in women with hyperandrogenemia such as PCOS.
authors.affiliation: Department of Physiology and Biophysics, Women's Health Research Center.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Maranon
authors.affiliation: Department of Physiology and Biophysics, Women's Health Research Center.
authors.forename: Roberta
authors.initials: R
authors.lastname: Lima
authors.affiliation: Department of Physiology and Biophysics, Women's Health Research Center, Cardiovascular Renal Research Center, and.
authors.forename: Frank T
authors.initials: FT
authors.lastname: Spradley
authors.affiliation: Department of Physiology and Biophysics, Women's Health Research Center, Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Jussara M
authors.initials: JM
authors.lastname: do Carmo
authors.affiliation: Department of Radiology.
authors.forename: Howei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Radiology.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
authors.affiliation: Department of Physiology and Biophysics, Women's Health Research Center.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bui
authors.affiliation: Department of Physiology and Biophysics.
authors.forename: R Lucas
authors.initials: RL
authors.lastname: Thomas
authors.affiliation: Department of Physiology and Biophysics, Women's Health Research Center.
authors.forename: Mohadetheh
authors.initials: M
authors.lastname: Moulana
authors.affiliation: Department of Physiology and Biophysics, Cardiovascular Renal Research Center, and Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: John E
authors.initials: JE
authors.lastname: Hall
authors.affiliation: Department of Physiology and Biophysics, Women's Health Research Center, Cardiovascular Renal Research Center, and.
authors.forename: Joey P
authors.initials: JP
authors.lastname: Granger
authors.affiliation: Department of Physiology and Biophysics, Women's Health Research Center, Cardiovascular Renal Research Center, and jreckelhoff@umc.edu.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Reckelhoff
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D013196:Dihydrotestosterone; D004195:Disease Models, Animal; D005260:Female; D006727:Hormone Antagonists; D017588:Hyperandrogenism / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation*; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology* / Q000601:surgery; D013997:Time Factors
chemical_list: D018674:Adrenergic Antagonists; D006727:Hormone Antagonists; D044105:Receptor, Melanocortin, Type 4; D013196:Dihydrotestosterone
keywords: dihydrotestosterone; female; hypertension; melanocortins; renal denervation; sympathetic nervous systen