Role of Estradiol Receptor Alpha in the Sexual Dimorphism of the Cardiorespiratory Effects of Sleep Apnea Syndrome via the Sympathetic Nervous System
Authors List
Aka Ella1,2,3, Marcouiller François1,2,3, Joseph Vincent1,2,3
1 Department of Medicine, Research Center of the University of cardiology and pneumology of Quebec, Laval University
2 Laval University
3 Quebec City, Quebec, Canada
Introduction
Intermittent hypoxia (IH), a major feature of obstructive sleep apnea syndrome (SAS), is associated with conditions such as hypertension and increased peripheral chemoreceptor activity. There is a correlation between the severity of SAS and the prevalence of hypertension and in men with SAS, more severe forms of hypertension compared to women, suggesting possible hormonal protection in women. Estradiol prevents hypertension and respiratory problems caused by IH. Its protective effects are done through the estradiol receptor alpha ERα. The central and peripheral regions of the sympathetic nervous system (SNS) involved in the regulation of sympathetic neuronal activity and blood pressure express ERα in both males and females.
Our general hypothesis is that ERα determines the sexual dimorphism of the cardiorespiratory effects of SAS through its action in the SNS.
Methodology
We use a mouse model of SAS: male and female mice, of wild types or deleted for the gene of ERα (KO), exposed or not to IH. The non-invasive tail cuff method allows the measurement of arterial blood pressure (BP). Whole-body plethysmography provides information on respiratory parameters and respiratory rhythm stability in the unconstrained animal. The ECG to calculate the different components of heart rate variability, reflecting SNS activation.
Results
Our preliminary results seem to suggest a male and female difference for BP, respiratory parameters and the occurrence of apneas and sighs indicating the stability of the respiratory rhythm. When comparing WT versus KO ratios, the males display a hyperventilation as a result of increased peripheral chemoreceptor activity, which is exacerbated by exposure to intermittent hypoxia. Males also display an increased heart rate variability compared to females.
Conclusion
Although preliminary, these data encourage us to complete our experimental groups in order to obtain statistically robust results. We plan to subsequently evaluate oxidative stress, a consequence of IH, in SNS structures. The data obtained from this project will fill an important gap in our knowledge of the interactions between hormonal systems and the consequences of intermittent hypoxia in male and female animals. This will allow us to better understand why men and women with SAS develop distinct cardiorespiratory consequences. This work may also help to better understand the underlying mechanisms linking menopause and the occurrence of sleep apnea in women and highlight a potential benefit of hormone therapy.
Research funding Source: Canadian Institutes of Health Research
Aka Ella1,2,3, Marcouiller François1,2,3, Joseph Vincent1,2,3
1 Department of Medicine, Research Center of the University of cardiology and pneumology of Quebec, Laval University
2 Laval University
3 Quebec City, Quebec, Canada
Introduction
Intermittent hypoxia (IH), a major feature of obstructive sleep apnea syndrome (SAS), is associated with conditions such as hypertension and increased peripheral chemoreceptor activity. There is a correlation between the severity of SAS and the prevalence of hypertension and in men with SAS, more severe forms of hypertension compared to women, suggesting possible hormonal protection in women. Estradiol prevents hypertension and respiratory problems caused by IH. Its protective effects are done through the estradiol receptor alpha ERα. The central and peripheral regions of the sympathetic nervous system (SNS) involved in the regulation of sympathetic neuronal activity and blood pressure express ERα in both males and females.
Our general hypothesis is that ERα determines the sexual dimorphism of the cardiorespiratory effects of SAS through its action in the SNS.
Methodology
We use a mouse model of SAS: male and female mice, of wild types or deleted for the gene of ERα (KO), exposed or not to IH. The non-invasive tail cuff method allows the measurement of arterial blood pressure (BP). Whole-body plethysmography provides information on respiratory parameters and respiratory rhythm stability in the unconstrained animal. The ECG to calculate the different components of heart rate variability, reflecting SNS activation.
Results
Our preliminary results seem to suggest a male and female difference for BP, respiratory parameters and the occurrence of apneas and sighs indicating the stability of the respiratory rhythm. When comparing WT versus KO ratios, the males display a hyperventilation as a result of increased peripheral chemoreceptor activity, which is exacerbated by exposure to intermittent hypoxia. Males also display an increased heart rate variability compared to females.
Conclusion
Although preliminary, these data encourage us to complete our experimental groups in order to obtain statistically robust results. We plan to subsequently evaluate oxidative stress, a consequence of IH, in SNS structures. The data obtained from this project will fill an important gap in our knowledge of the interactions between hormonal systems and the consequences of intermittent hypoxia in male and female animals. This will allow us to better understand why men and women with SAS develop distinct cardiorespiratory consequences. This work may also help to better understand the underlying mechanisms linking menopause and the occurrence of sleep apnea in women and highlight a potential benefit of hormone therapy.
Research funding Source: Canadian Institutes of Health Research
