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Am J Physiol Heart Circ Physiol. 2019 Nov 1. doi: 10.1152/ajpheart.00350.2019. [Epub ahead of print]

Caspase Lesions of PVN-Projecting MnPO Neurons Blocks the Sustained Component of CIH-Induced Hypertension in Adult Male Rats.

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Phsyiology and Anatomy, Univ. North Texas Health Sciences Center - Fort Worth, Algeria.
Department of Physiology and Anatomy, University of North Texas Health Science Center, United States.
Department of Physiology and Anatomy, Univ. North Texas Health Sciences Center - Fort Worth, United States.


Obstructive Sleep Apnea is characterized by interrupted breathing that leads to cardiovascular sequelae including chronic hypertension that can persist into waking hours. Chronic intermittent hypoxia, 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 pre-autonomic 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 (250-300g) were anesthetized with isoflurane and stereotaxically injected bilaterally in the PVN with a retrograde Cre-containing 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 advanced oxidative protein products levels 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.


angiotensin; hypertension; hypoxia; preoptic area; sleep apnea

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