Ventilatory, metabolic, and thermal responses to hypercapnia in female rats: effects of estrous cycle, ovariectomy, and hormonal replacement

J Appl Physiol (1985). 2015 Jul 1;119(1):61-8. doi: 10.1152/japplphysiol.00254.2015. Epub 2015 Apr 30.


The aim of this study was to examine how estrous cycle, ovariectomy, and hormonal replacement affect the respiratory [ventilation (V̇e), tidal volume, and respiratory frequency], metabolic (V̇o2), and thermoregulatory (body temperature) responses to hypercapnia (7% CO2) in female Wistar rats. The parameters were measured in rats during different phases of the estrous cycle, and also in ovariectomized (OVX) rats supplemented with 17β-estradiol (OVX+E2), with a combination of E2 and progesterone (OVX+E2P), or with corn oil (OVX+O, vehicle). All experiments were conducted on day 8 after ovariectomy. The intact animals did not present alterations during normocapnia or under hypercapnia in V̇e, tidal volume, respiratory frequency, V̇o2, and V̇e/V̇o2 in the different phases of the estrous cycle. However, body temperature was higher in female rats on estrus. Hormonal replacement did not change the ventilatory, thermoregulatory, or metabolic parameters during hypercapnia, compared with the OVX animals. Nevertheless, OVX+E2, OVX+E2P, and OVX+O presented lower hypercapnic ventilatory responses compared with intact females on the day of estrus. Also, rats in estrus showed higher V̇e and V̇e/V̇o2 during hypercapnia than OVX animals. The data suggest that other gonadal factors, besides E2 and P, are possibly involved in these responses.

Keywords: CO2; breathing; cycling rats; estrogen; progesterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Temperature Regulation*
  • Carbon Dioxide / blood
  • Estradiol / blood
  • Estradiol / pharmacology
  • Estrous Cycle*
  • Female
  • Hormone Replacement Therapy*
  • Hypercapnia / metabolism*
  • Hypercapnia / physiopathology*
  • Ovariectomy*
  • Oxygen Consumption
  • Progesterone / blood
  • Progesterone / pharmacology
  • Rats
  • Rats, Wistar
  • Respiratory Mechanics*
  • Tidal Volume / drug effects
  • Vagina / cytology
  • Vagina / drug effects


  • Carbon Dioxide
  • Progesterone
  • Estradiol