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Caspase lesions of PVN-projecting MnPO neurons block the sustained component of CIH-induced hypertension in adult male rats
- Source :
- Am J Physiol Heart Circ Physiol
- Publication Year :
- 2019
- Publisher :
- American Physiological Society, 2019.
-
Abstract
- Obstructive sleep apnea is characterized by interrupted breathing that leads to cardiovascular sequelae including chronic hypertension that can persist into the waking hours. Chronic intermittent hypoxia (CIH), which models the hypoxemia associated with sleep apnea, is sufficient to cause a sustained increase in blood pressure that involves the central nervous system. The median preoptic nucleus (MnPO) is an integrative forebrain region that contributes to blood pressure regulation and neurogenic hypertension. The MnPO projects to the paraventricular nucleus (PVN), a preautonomic region. We hypothesized that pathway-specific lesions of the projection from the MnPO to the PVN would attenuate the sustained component of chronic intermittent hypoxia-induced hypertension. Adult male Sprague-Dawley rats (250–300 g) were anesthetized with isoflurane and stereotaxically injected bilaterally in the PVN with a retrograde Cre-containing adeno-associated virus (AAV; AAV9.CMV.HI.eGFP-Cre.WPRE.SV40) and injected in the MnPO with caspase-3 (AAV5-flex-taCasp3-TEVp) or control virus (AAV5-hSyn-DIO-mCherry). Three weeks after the injections the rats were exposed to a 7-day intermittent hypoxia protocol. During chronic intermittent hypoxia, controls developed a diurnal hypertension that was blunted in rats with caspase lesions. Brain tissue processed for FosB immunohistochemistry showed decreased staining with caspase-induced lesions of MnPO and downstream autonomic-regulating nuclei. Chronic intermittent hypoxia significantly increased plasma levels of advanced oxidative protein products in controls, but this increase was blocked in caspase-lesioned rats. The results indicate that PVN-projecting MnPO neurons play a significant role in blood pressure regulation in the development of persistent chronic intermittent hypoxia hypertension.NEW & NOTEWORTHY Chronic intermittent hypoxia associated with obstructive sleep apnea increases oxidative stress and leads to chronic hypertension. Sustained hypertension may be mediated by angiotensin II-induced neural plasticity of excitatory median preoptic neurons in the forebrain that project to the paraventricular nucleus of the hypothalamus. Selective caspase lesions of these neurons interrupt the drive for sustained hypertension and cause a reduction in circulating oxidative protein products. This indicates that a functional connection between the forebrain and hypothalamus is necessary to drive diurnal hypertension associated with intermittent hypoxia. These results provide new information about central mechanisms that may contribute to neurogenic hypertension.
- Subjects :
- Male
medicine.medical_specialty
Adult male
Physiology
Apoptosis
medicine.disease_cause
Rats, Sprague-Dawley
Heart Rate
Physiology (medical)
Internal medicine
Renin–angiotensin system
Medicine
Animals
Arterial Pressure
Hypoxia
Caspase
biology
business.industry
Caspase 3
Sleep apnea
Hypoxia (medical)
medicine.disease
Preoptic Area
Circadian Rhythm
Preoptic area
Obstructive sleep apnea
Disease Models, Animal
Oxidative Stress
Endocrinology
Hypertension
biology.protein
medicine.symptom
Cardiology and Cardiovascular Medicine
business
Proto-Oncogene Proteins c-fos
Oxidative stress
Research Article
Paraventricular Hypothalamic Nucleus
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Am J Physiol Heart Circ Physiol
- Accession number :
- edsair.doi.dedup.....fb0e27608389d5149f4c6f2e4c35796e