Sex Differences in Blood Pressure Response to Intermittent Hypoxia in Rats

Hinojosa‐Laborde, Carmen; Mifflin, Steve

doi:10.1161/01.hyp.0000175477.33816.f3

Cited by 75 publications

(84 citation statements)

References 29 publications

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confidence: 64%

“…enhances CB chemosensory discharge in normoxia and in response to hypoxia. 12,19,[23][24][25] Furthermore, it has been shown that arterial blood pressure (BP) rapidly increases after 3 to 4 days after CIH exposure, 14,[26][27][28] which is consistent with the time required to potentiate the neural discharges from the CB chemoreceptor during CIH .19,24 Despite all the advances related to the contribution of CB chemoreception to the cardiovascular consequences of CIH, there are no studies showing the role played by the CB chemoreflex once the hypertensive phenotype has become expressed because of CIH exposure. It is worth noting that it is fundamental from a translational perspective because in previous studies performed by Fletcher et al,20 the CBs were removed before the start of CIH and, therefore, before the development of systemic hypertension.…”

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confidence: 99%

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Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

et al. 2016

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The obstructive sleep apnea (OSA), a worldwide sleep breathing disorder that affect 9% of women and 24% of adult men, 1 is an independent risk factor for systemic hypertension and stroke and is associated with atrial arrhythmogenesis. [2][3][4][5][6] Chronic intermittent hypoxia (CIH), which is the principal feature of OSA, is considered the main factor for the hypertension.2-4,7 CIH produces autonomic dysfunction characterized by sympathetic hyperactivity, alterations of heart rate (HR) variability (HRV), and reduction of cardiac baroreflex efficiency. [8][9][10][11][12][13][14] Although the link between OSA and hypertension is well established, the mechanisms responsible for the autonomic imbalance and the hypertension are not entirely known. CIH produces oxidative stress, inflammation, and endothelial dysfunction that contribute to the hypertension. [2][3][4]7 However, a growing body of evidences suggests that the carotid body (CB), the main oxygen chemoreceptor organ, 15 plays a crucial role in the development of autonomic alterations and hypertension after CIH. Indeed, patients with OSA and animals exposed to CIH show enhanced cardiorespiratory and sympathetic responses to hypoxia, suggesting that CIH potentiates the CB-mediated chemoreflex drive. 7,13,[16][17][18][19] found that bilateral CB denervation before the CIH exposure prevents the development of the hypertension in rats. Despite this important result, the idea that the CB chemoreceptor contributes to the progression of cardiovascular pathologies associated with OSA was not seriously considered until the last decade. Indeed, in the last years, the proposal that the CB is involved in the progression of the CIH-induced hypertension received further attention . 3,4,7,18,21,22 Neural recordings of CB chemosensory activity have shown that CIH selectively Abstract-Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) chemosensory responses to hypoxia and produces autonomic dysfunction, cardiac arrhythmias, and hypertension. We tested whether autonomic alterations, arrhythmogenesis, and the progression of hypertension induced by CIH depend on the enhanced CB chemosensory drive, by ablation of the CB chemoreceptors. Male Sprague-Dawley rats were exposed to control (Sham) conditions for 7 days and then to CIH (5% O 2 , 12/h 8 h/d) for a total of 28 days. At 21 days of CIH exposure, rats underwent bilateral CB ablation and then exposed to CIH for 7 additional days. Arterial blood pressure and ventilatory chemoreflex response to hypoxia were measured in conscious rats. In addition, cardiac autonomic imbalance, cardiac baroreflex gain, and arrhythmia score were assessed during the length of the experiments.In separate experimental series, we measured extracellular matrix remodeling content in cardiac atrial tissue and systemic oxidative stress. CIH induced hypertension, enhanced ventilatory response to hypoxia, induced autonomic imbalance toward sympathetic preponderance, reduced baroreflex gain, and inc...

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confidence: 99%

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

et al. 2016

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“…The multitude of consequences of intermittent hypoxia may be influenced by age and gender, depending on the experimental paradigm and the specific physiologic consequence. [26][27][28] Whether the results are representative of the findings in women or in other races cannot be determined from the study. The lack of improvement in any of the secondary outcomes, including reactive hyperemia index was intriguing.…”

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confidence: 91%

Commentary on CPAP vs. Oxygen for Treatment of OSA

Shafazand

Badr

2014

Journal of Clinical Sleep Medicine

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In individuals with cardiovascular (CV) disease or multiple CV risk factors and obstructive sleep apnea (OSA), does the 12 week use of continuous positive airway pressure (CPAP) therapy vs. nocturnal oxygen vs. sleep and lifestyle education (control) improve the 24-hour ambulatory mean blood pressure? Methods DesignMulti-center, randomized, controlled trial; clinicaltrials.gov Identifi er: NCT01086800. AllocationRandomization was performed centrally via a web-based system, using a stratifi ed permuted block design. The randomization sequence was concealed. Allocation was stratifi ed by recruitment site and by the presence of coronary artery disease. BlindingThe investigators and participants were not blinded to study arm assignment. Clinical site staff, performing ambulatory blood pressure testing, and coordinating center staff, editing and scoring the blood pressure recordings, were blinded to group assignment. Follow-up period3 months. SettingParticipants were recruited from cardiology clinics at four participating US medical centers and were screened for OSA using the Berlin questionnaire, followed by home sleep testing for eligible patients. Subjects318 participants were randomly assigned to healthy lifestyle and sleep education alone (HLSE -control; n = 106), or CPAP and HLSE (n = 106) or nocturnal oxygen (NSO) and HLSE (n = 106). The mean age of participants was HLSE: 63. CPAP: 63.5 ± 7.0, and NSO: 62.9 ± 7.3. More than 69% of participants were male and white, mean BMI range was 33.0 to 34.7 and the mean AHI range was 24.0 ± 8.1 (NSO) to 25.5 ± 8.8 (HLSE). Majority of patients were on an Ace-inhibitor or ARB or β blocker, more than 50% had a history of coronary artery disease (CAD), 88% had hypertension. Blood pressure was generally well controlled at baseline.Inclusion Criteria: 1) Age 45-75 years; 2) High risk for CVD event, defi ned by: a) established stable CAD or b) 3 or more established CVD risk factors, e.g., hypertension (treated by a physician or systolic BP > 140 or diastolic BP > 90), diabetes mellitus, BMI > 30, total cholesterol > 240 or LDL cholesterol > 160 or being treated for dyslipidemia; 3) Berlin score ≥ 2; 4) Home sleep study confi rmed OSA defi ned as AHI ≥ 15.Exclusion Criteria: 1) Congestive heart failure with a cardiac ejection fraction of < 35% or NYHA class ≥ 2; 2) poorly controlled HTN (> 170/ > 110), poorly controlled diabetes, stroke with functional impairment or other poorly controlled co-morbidities; 3) severe chronic insomnia or circadian rhythm disorder; 4) severe sleepiness with an Epworth Sleepiness Score of ≥ 16; 5) resting oxygen saturation < 90%; 6) pregnancy; 7) using oxygen or past use of prescribed CPAP or BiPAP for sleep apnea; 8) Had upper airway surgery (UPPP) for snoring or sleep apnea; 9) AHI > 50, central sleep apnea index > 5, nocturnal oxygen saturation < 85% for > 10% of sleep record. InterventionPatients meeting eligibility criteria were randomized to HLSE (control), CPAP and HLSE, or NSO and HLSE for 12 weeks. Auto-titrating CPAP was used for treatment o...

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“…In addition to the differences in hypoxic protocols, afferent inputs, and behavioural state, sex-dependent differences may play an additional role. Hinojosa-Laborde and Mifflin [40] reported the rise of HR after exposure to intermittent hypoxia in males but not in females, where the response could even be the reverse.…”

Section: The Effects Of Ld Cycle On the Cardiovascular Reactivity In mentioning

confidence: 97%

Heart-rate changes in asphyxic preconditioning in rats depend on light-dark cycle

et al. 2011

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AbstractGenerally, it is assumed that heart-rhythm disorders during hypoxia result from the interplay between the autonomic nervous system (ANS) and the direct effect of hypoxia on cardiorespiratory structures of the central nervous system and on the myocardium. Circadian variability in the ANS may substantially influence the electrical stability of the myocardium, and thus it is associated with the preconditioning protective mechanism. We designed our study using anaesthetized Wistar rats (ketamine/xylazine 100 mg/15 mg/kg, i.m., open chest experiments) to evaluate the effect of preconditioning (PC) induced by 1 to 3 cycles (1 PC–3 PC) of asphyxia (5 min. of artificial hypoventilation, VT = 0.5 ml/100 g of b.w., 20 breaths/min.) and reoxygenation (5 min. of artificial ventilation, VT = 1 ml/100 g of b.w., 50 breaths/min.) on the heart rate (HR) during followed exposure 20 minutes of hypoventilation after adaptation to a light-dark (LD) cycle of 12 hours:12 hours. Hypoxic HR increases were only minimally prevented by 1 to 2 PC pre-treatment, particularly during the dark part of the day. A statistically significant HR increase required 3 PC and was seen only in the light part of the day. We concluded that possible ANS participation in asphyxic preconditioning depends not only on the number of preconditioned cycles but also on the LD cycle, when the ANS participation in preconditioning can be effective only in the light (nonactive) period.

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Sex Differences in Blood Pressure Response to Intermittent Hypoxia in Rats

Cited by 75 publications

References 29 publications

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

Carotid Body Ablation Abrogates Hypertension and Autonomic Alterations Induced by Intermittent Hypoxia in Rats

Commentary on CPAP vs. Oxygen for Treatment of OSA

Heart-rate changes in asphyxic preconditioning in rats depend on light-dark cycle

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