Hypoxia-inducible factors and hypertension: lessons from sleep apnea syndrome

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Jayasri NanduriNanduri R Prabhakar

Abstract

Systemic hypertension is one of the most prevalent cardiovascular diseases. Sleep-disordered breathing (SDB) with recurrent apnea is a major risk factor for developing essential hypertension. Chronic intermittent hypoxia (CIH) is a hallmark manifestation of recurrent apnea. Rodent models patterned after the O2 profiles seen with SDB patients showed that CIH is the major stimulus for causing systemic hypertension. This article reviews the physiological and molecular basis of CIH-induced hypertension. Physiological studies have identified that augmented carotid body chemosensory reflex and the resulting increase in sympathetic nerve activity are major contributors to CIH-induced hypertension. Analysis of molecular mechanisms revealed that CIH activates hypoxia-inducible factor (HIF)-1 and suppresses HIF-2-mediated transcription. Dysregulation of HIF-1- and HIF-2-mediated transcription leads to imbalance of pro-oxidant and anti-oxidant enzyme gene expression resulting in increased reactive oxygen species (ROS) generation in the chemosensory reflex which is central for developing hypertension.

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Citations

Feb 20, 2016·Current Hypertension Reports·Farhanah Yousaf, Bruce Spinowitz
Jan 12, 2016·The Journal of Physiology·M QuinteroT Agapito
May 10, 2018·The Journal of Physiology·Jan Marino RamirezIbis M Agosto-Marlin
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Apr 30, 2021·Nature and Science of Sleep·Hong Peng LiQing Yun Li
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Aug 28, 2021·Frontiers in Cardiovascular Medicine·Emilio Y Lucero García RojasRichard A Bond
Jul 24, 2021·Physiological Genomics·Jayasri NanduriNanduri R Prabhakar

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