Angiotensin type 1a receptors in the median preoptic nucleus support intermittent hypoxia-induced hypertension

Brent Shell, George E. Farmer, T. Prashant Nedungadi, Lei A. Wang, Alexandria B. Marciante, Brina Snyder, Rebecca Lynn Cunningham, Joseph Thomas Cunningham

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Chronic intermittent hypoxia (CIH) is a model of the hypoxemia from sleep apnea that causes a sustained increase in blood pressure. Inhibition of the central renin-angiotensin system or FosB in the median preoptic nucleus (MnPO) prevents the sustained hypertensive response to CIH. We tested the hypothesis that angiotensin type 1a (AT1a) receptors in the MnPO, which are upregulated by CIH, contribute to this hypertension. In preliminary experiments, retrograde tract tracing studies showed AT1a receptor expression in MnPO neurons projecting to the paraventricular nucleus. Adult male rats were exposed to 7 days of intermittent hypoxia (cycling between 21% and 10% O2 every 6 min, 8 h/day during light phase). Seven days of CIH was associated with a FosB-dependent increase in AT1a receptor mRNA without changes in the permeability of the blood-brain barrier in the MnPO. Separate groups of rats were injected in the MnPO with an adeno-associated virus containing short hairpin (sh)RNA against AT1a receptors to test their role in intermittent hypoxia hypertension. Injections of shRNA against AT1a in MnPO blocked the increase in mRNA associated with CIH, prevented the sustained component of the hypertension during normoxia, and reduced circulating advanced oxidation protein products, an indicator of oxidative stress. Rats injected with shRNA against AT1a and exposed to CIH had less FosB staining in MnPO and the rostral ventrolateral medulla after intermittent hypoxia than rats injected with the control vector that were exposed to CIH. Our results indicate AT1a receptors in the MnPO contribute to the sustained blood pressure increase to intermittent hypoxia.

Original languageEnglish
Pages (from-to)R651-R665
JournalAmerican journal of physiology. Regulatory, integrative and comparative physiology
Volume316
Issue number5
DOIs
StatePublished - 1 May 2019

Fingerprint

Angiotensin Type 1 Receptor
Preoptic Area
Hypertension
Small Interfering RNA
Angiotensins
Hypoxia
Advanced Oxidation Protein Products
Blood Pressure
Dependovirus
Messenger RNA
Paraventricular Hypothalamic Nucleus
Sleep Apnea Syndromes
Renin-Angiotensin System
Blood-Brain Barrier
Permeability
Oxidative Stress

Keywords

  • angiotensin
  • hypertension
  • sleep apnea

Cite this

Shell, Brent ; Farmer, George E. ; Nedungadi, T. Prashant ; Wang, Lei A. ; Marciante, Alexandria B. ; Snyder, Brina ; Cunningham, Rebecca Lynn ; Cunningham, Joseph Thomas. / Angiotensin type 1a receptors in the median preoptic nucleus support intermittent hypoxia-induced hypertension. In: American journal of physiology. Regulatory, integrative and comparative physiology. 2019 ; Vol. 316, No. 5. pp. R651-R665.
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abstract = "Chronic intermittent hypoxia (CIH) is a model of the hypoxemia from sleep apnea that causes a sustained increase in blood pressure. Inhibition of the central renin-angiotensin system or FosB in the median preoptic nucleus (MnPO) prevents the sustained hypertensive response to CIH. We tested the hypothesis that angiotensin type 1a (AT1a) receptors in the MnPO, which are upregulated by CIH, contribute to this hypertension. In preliminary experiments, retrograde tract tracing studies showed AT1a receptor expression in MnPO neurons projecting to the paraventricular nucleus. Adult male rats were exposed to 7 days of intermittent hypoxia (cycling between 21{\%} and 10{\%} O2 every 6 min, 8 h/day during light phase). Seven days of CIH was associated with a FosB-dependent increase in AT1a receptor mRNA without changes in the permeability of the blood-brain barrier in the MnPO. Separate groups of rats were injected in the MnPO with an adeno-associated virus containing short hairpin (sh)RNA against AT1a receptors to test their role in intermittent hypoxia hypertension. Injections of shRNA against AT1a in MnPO blocked the increase in mRNA associated with CIH, prevented the sustained component of the hypertension during normoxia, and reduced circulating advanced oxidation protein products, an indicator of oxidative stress. Rats injected with shRNA against AT1a and exposed to CIH had less FosB staining in MnPO and the rostral ventrolateral medulla after intermittent hypoxia than rats injected with the control vector that were exposed to CIH. Our results indicate AT1a receptors in the MnPO contribute to the sustained blood pressure increase to intermittent hypoxia.",
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Angiotensin type 1a receptors in the median preoptic nucleus support intermittent hypoxia-induced hypertension. / Shell, Brent; Farmer, George E.; Nedungadi, T. Prashant; Wang, Lei A.; Marciante, Alexandria B.; Snyder, Brina; Cunningham, Rebecca Lynn; Cunningham, Joseph Thomas.

In: American journal of physiology. Regulatory, integrative and comparative physiology, Vol. 316, No. 5, 01.05.2019, p. R651-R665.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Angiotensin type 1a receptors in the median preoptic nucleus support intermittent hypoxia-induced hypertension

AU - Shell, Brent

AU - Farmer, George E.

AU - Nedungadi, T. Prashant

AU - Wang, Lei A.

AU - Marciante, Alexandria B.

AU - Snyder, Brina

AU - Cunningham, Rebecca Lynn

AU - Cunningham, Joseph Thomas

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AB - Chronic intermittent hypoxia (CIH) is a model of the hypoxemia from sleep apnea that causes a sustained increase in blood pressure. Inhibition of the central renin-angiotensin system or FosB in the median preoptic nucleus (MnPO) prevents the sustained hypertensive response to CIH. We tested the hypothesis that angiotensin type 1a (AT1a) receptors in the MnPO, which are upregulated by CIH, contribute to this hypertension. In preliminary experiments, retrograde tract tracing studies showed AT1a receptor expression in MnPO neurons projecting to the paraventricular nucleus. Adult male rats were exposed to 7 days of intermittent hypoxia (cycling between 21% and 10% O2 every 6 min, 8 h/day during light phase). Seven days of CIH was associated with a FosB-dependent increase in AT1a receptor mRNA without changes in the permeability of the blood-brain barrier in the MnPO. Separate groups of rats were injected in the MnPO with an adeno-associated virus containing short hairpin (sh)RNA against AT1a receptors to test their role in intermittent hypoxia hypertension. Injections of shRNA against AT1a in MnPO blocked the increase in mRNA associated with CIH, prevented the sustained component of the hypertension during normoxia, and reduced circulating advanced oxidation protein products, an indicator of oxidative stress. Rats injected with shRNA against AT1a and exposed to CIH had less FosB staining in MnPO and the rostral ventrolateral medulla after intermittent hypoxia than rats injected with the control vector that were exposed to CIH. Our results indicate AT1a receptors in the MnPO contribute to the sustained blood pressure increase to intermittent hypoxia.

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M3 - Article

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