Age and estrogen-associated reductions in hypoxic ventilatory response and chemosensitivity in female rats

Respiratory function is modulated by circulating steroid hormones. In female rats, steroid hormones fluctuate across the normal estrous cycle and decline with age, similar to human menopause. To determine the influence of steroid hormones, and mimic aspects of age-related reductions in hormones, the...

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Main Authors: Jessica M. L. Grittner, Rebecca Barok, Edgar Juarez Lopez, Misha Shah, Brendan J. Dougherty
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Physiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2024.1511960/full
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author Jessica M. L. Grittner
Rebecca Barok
Edgar Juarez Lopez
Misha Shah
Brendan J. Dougherty
author_facet Jessica M. L. Grittner
Rebecca Barok
Edgar Juarez Lopez
Misha Shah
Brendan J. Dougherty
author_sort Jessica M. L. Grittner
collection DOAJ
description Respiratory function is modulated by circulating steroid hormones. In female rats, steroid hormones fluctuate across the normal estrous cycle and decline with age, similar to human menopause. To determine the influence of steroid hormones, and mimic aspects of age-related reductions in hormones, the ovariectomy model is often employed. Ovariectomy (OVX) induces an immediate and persistent decrease in steroid hormones. The current study aimed to interrogate whether the OVX model of hormone reduction impacted specific aspects of respiratory function [chemosensitivity and the hypoxic ventilatory response (HVR)] in a manner consistent with natural age-related declines in hormones. Using barometric plethysmography, three experimental groups of female rats were assessed for HVR, chemosensitivity, and respiratory neural drive during progressive hypoxic challenges (FIO2: 0.15, 0.12, and 0.09): young (3–5 mos. old; in proestrus; n = 10), young OVX (3–5 mos. old; n = 10), and aged (>20 mos. old; n = 10). Our findings indicted that sex hormone loss did not appear to impact chemosensitivity or neural drive. Natural aging, but not OVX, resulted in decreased HVR as well as reduced magnitude in ventilatory output during stepwise hypoxia. Differences in metabolism were important to the interpretation of these results. Collectively, these data support the concept that aging impacts female respiratory function in complex and unique ways that differ from OVX.
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spelling doaj-art-868fc051491e4e1fa067effba645cd052025-01-28T06:40:49ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-01-011510.3389/fphys.2024.15119601511960Age and estrogen-associated reductions in hypoxic ventilatory response and chemosensitivity in female ratsJessica M. L. Grittner0Rebecca Barok1Edgar Juarez Lopez2Misha Shah3Brendan J. Dougherty4Rehabilitation Science Graduate Program, Department of Family Medicine and Community Health, University of Minnesota Medical School, Minneapolis, MN, United StatesRehabilitation Science Graduate Program, Department of Family Medicine and Community Health, University of Minnesota Medical School, Minneapolis, MN, United StatesDivision of Physical Therapy and Rehabilitation Science, Department of Family Medicine and Community Health, University of Minnesota Medical School, Minneapolis, MN, United StatesCollege of Biological Sciences, University of Minnesota, Minneapolis, MN, United StatesDivision of Physical Therapy and Rehabilitation Science, Department of Family Medicine and Community Health, University of Minnesota Medical School, Minneapolis, MN, United StatesRespiratory function is modulated by circulating steroid hormones. In female rats, steroid hormones fluctuate across the normal estrous cycle and decline with age, similar to human menopause. To determine the influence of steroid hormones, and mimic aspects of age-related reductions in hormones, the ovariectomy model is often employed. Ovariectomy (OVX) induces an immediate and persistent decrease in steroid hormones. The current study aimed to interrogate whether the OVX model of hormone reduction impacted specific aspects of respiratory function [chemosensitivity and the hypoxic ventilatory response (HVR)] in a manner consistent with natural age-related declines in hormones. Using barometric plethysmography, three experimental groups of female rats were assessed for HVR, chemosensitivity, and respiratory neural drive during progressive hypoxic challenges (FIO2: 0.15, 0.12, and 0.09): young (3–5 mos. old; in proestrus; n = 10), young OVX (3–5 mos. old; n = 10), and aged (>20 mos. old; n = 10). Our findings indicted that sex hormone loss did not appear to impact chemosensitivity or neural drive. Natural aging, but not OVX, resulted in decreased HVR as well as reduced magnitude in ventilatory output during stepwise hypoxia. Differences in metabolism were important to the interpretation of these results. Collectively, these data support the concept that aging impacts female respiratory function in complex and unique ways that differ from OVX.https://www.frontiersin.org/articles/10.3389/fphys.2024.1511960/fullhypoxic ventilatory response (HVR)chemosensitivityestrogenagingstepwise hypoxiarespiratory physiology
spellingShingle Jessica M. L. Grittner
Rebecca Barok
Edgar Juarez Lopez
Misha Shah
Brendan J. Dougherty
Age and estrogen-associated reductions in hypoxic ventilatory response and chemosensitivity in female rats
Frontiers in Physiology
hypoxic ventilatory response (HVR)
chemosensitivity
estrogen
aging
stepwise hypoxia
respiratory physiology
title Age and estrogen-associated reductions in hypoxic ventilatory response and chemosensitivity in female rats
title_full Age and estrogen-associated reductions in hypoxic ventilatory response and chemosensitivity in female rats
title_fullStr Age and estrogen-associated reductions in hypoxic ventilatory response and chemosensitivity in female rats
title_full_unstemmed Age and estrogen-associated reductions in hypoxic ventilatory response and chemosensitivity in female rats
title_short Age and estrogen-associated reductions in hypoxic ventilatory response and chemosensitivity in female rats
title_sort age and estrogen associated reductions in hypoxic ventilatory response and chemosensitivity in female rats
topic hypoxic ventilatory response (HVR)
chemosensitivity
estrogen
aging
stepwise hypoxia
respiratory physiology
url https://www.frontiersin.org/articles/10.3389/fphys.2024.1511960/full
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