Roles for the sympathetic nervous system, renal nerves, and CNS melanocortin-4 receptor in the elevated blood pressure in hyperandrogenemic female rats.

نویسندگان

  • Rodrigo Maranon
  • Roberta Lima
  • Frank T Spradley
  • Jussara M do Carmo
  • Howei Zhang
  • Andrew D Smith
  • Elizabeth Bui
  • R Lucas Thomas
  • Mohadetheh Moulana
  • John E Hall
  • Joey P Granger
  • Jane F Reckelhoff
چکیده

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.

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1 Roles for the sympathetic nervous system , renal nerves , and 2 CNS melanocortin - 4 receptor in the elevated blood pressure 3 in hyperandrogenemic female rats

Running title: Hypertension in Hyperandrogenemic Female Rats. 21 22 Corresponding author: 23 Jane F. Reckelhoff, Ph.D. 24 Director, Women’s Health Research Center 25 University of Mississippi Medical Center 26 2500 N. State Street 27 Jackson, MS 39216-4505 28 Email: [email protected] 29 Phone: 601-984-1819 30 FAX: 601-984-1817 31 32 Articles in PresS. Am J Physiol Regul Integr Comp Physiol (F...

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عنوان ژورنال:
  • American journal of physiology. Regulatory, integrative and comparative physiology

دوره 308 8  شماره 

صفحات  -

تاریخ انتشار 2015