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Angiotensin converting enzyme 1 in the median preoptic nucleus contributes to chronic intermittent hypoxia hypertension. 2017

Katelynn E Faulk, and T Prashant Nedungadi, and J Thomas Cunningham
Institute for Cardiovascular and Metabolic Diseases, University of North Texas Health Science Centre at Fort Worth, Fort Worth, Texas.

Obstructive sleep apnea is associated with hypertension and cardiovascular disease. Chronic intermittent hypoxia is used to model the arterial hypoxemia seen in sleep apnea patients and is associated with increased sympathetic nerve activity and a sustained diurnal increase in blood pressure. The renin angiotensin system has been associated with hypertension seen in chronic intermittent hypoxia. Angiotensin converting enzyme 1, which cleaves angiotensin I to the active counterpart angiotensin II, is present within the central nervous system and has been shown to be regulated by AP-1 transcription factors, such as ΔFosB. Our previous study suggested that this transcriptional regulation in the median preoptic nucleus contributes to the sustained blood pressure seen following chronic intermittent hypoxia. Viral mediated delivery of a short hairpin RNA against angiotensin converting enzyme 1 in the median preoptic nucleus was used along with radio-telemetry measurements of blood pressure to test this hypothesis. FosB immunohistochemistry was utilized in order to assess the effects of angiotensin converting enzyme 1 knockdown on the activity of nuclei downstream from median preoptic nucleus. Angiotensin converting enzyme 1 knockdown within median preoptic nucleus significantly attenuated the sustained hypertension seen in chronic intermittent hypoxia. Angiotensin converting enzyme 1 seems to be partly responsible for regulating downstream regions involved in sympathetic and blood pressure control, such as the paraventricular nucleus and the rostral ventrolateral medulla. The data suggest that angiotensin converting enzyme 1 within median preoptic nucleus plays a critical role in the sustained hypertension seen in chronic intermittent hypoxia.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D007703 Peptidyl-Dipeptidase A A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of ANGIOTENSIN I to ANGIOTENSIN II, with increase in vasoconstrictor activity, but no action on angiotensin II. It is also able to inactivate BRADYKININ, a potent vasodilator; and has a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. (From https://www.uniprot.org April 15, 2020). ACE1 Angiotensin-Converting Enzyme 1,ACE1 Protein,Angiotensin Converting Enzyme,Angiotensin Converting Enzyme 1,Antigens, CD143,CD143 Antigens,Dipeptidyl Carboxypeptidase I,Kininase II,Peptidase P,Angiotensin I-Converting Enzyme,Carboxycathepsin,Dipeptidyl Peptidase A,Kininase A,ACE1 Angiotensin Converting Enzyme 1,Angiotensin I Converting Enzyme,Carboxypeptidase I, Dipeptidyl,Peptidyl Dipeptidase A
D008297 Male Males
D010286 Paraventricular Hypothalamic Nucleus Nucleus in the anterior part of the HYPOTHALAMUS. Hypothalamic Paraventricular Nucleus,Paraventricular Nucleus,Hypothalamic Nucleus, Paraventricular,Nucleus, Hypothalamic Paraventricular,Nucleus, Paraventricular,Nucleus, Paraventricular Hypothalamic,Paraventricular Nucleus, Hypothalamic
D011301 Preoptic Area Region of hypothalamus between the ANTERIOR COMMISSURE and OPTIC CHIASM. Area Preoptica,Lateral Preoptic Area,Medial Preoptic Area,Preoptic Nuclei,Area Preopticas,Area, Lateral Preoptic,Area, Medial Preoptic,Area, Preoptic,Areas, Lateral Preoptic,Areas, Medial Preoptic,Areas, Preoptic,Lateral Preoptic Areas,Medial Preoptic Areas,Nuclei, Preoptic,Nucleus, Preoptic,Preoptic Area, Lateral,Preoptic Area, Medial,Preoptic Areas,Preoptic Areas, Lateral,Preoptic Areas, Medial,Preoptic Nucleus,Preoptica, Area,Preopticas, Area
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000860 Hypoxia Sub-optimal OXYGEN levels in the ambient air of living organisms. Anoxia,Oxygen Deficiency,Anoxemia,Deficiency, Oxygen,Hypoxemia,Deficiencies, Oxygen,Oxygen Deficiencies
D012249 Rhombencephalon The posterior of the three primitive cerebral vesicles of an embryonic brain. It consists of myelencephalon, metencephalon, and isthmus rhombencephali from which develop the major BRAIN STEM components, such as MEDULLA OBLONGATA from the myelencephalon, CEREBELLUM and PONS from the metencephalon, with the expanded cavity forming the FOURTH VENTRICLE. Hindbrain,Hind Brain,Brain, Hind,Brains, Hind,Hind Brains,Hindbrains,Rhombencephalons
D016760 Proto-Oncogene Proteins c-fos Cellular DNA-binding proteins encoded by the c-fos genes (GENES, FOS). They are involved in growth-related transcriptional control. c-fos combines with c-jun (PROTO-ONCOGENE PROTEINS C-JUN) to form a c-fos/c-jun heterodimer (TRANSCRIPTION FACTOR AP-1) that binds to the TRE (TPA-responsive element) in promoters of certain genes. Fos B Protein,Fos-Related Antigen,Fos-Related Antigens,c-fos Protein,c-fos Proteins,fos Proto-Oncogene Protein,fos Proto-Oncogene Proteins,p55(c-fos),Antigens, Fos-Related,FRAs,Proto-Oncogene Products c-fos,Proto-Oncogene Proteins fos,p55 c-fos,Antigen, Fos-Related,Fos Related Antigen,Fos Related Antigens,Protein, c-fos,Protein, fos Proto-Oncogene,Proto Oncogene Products c fos,Proto Oncogene Proteins c fos,Proto Oncogene Proteins fos,Proto-Oncogene Protein, fos,c fos Protein,c fos Proteins,fos Proto Oncogene Protein,fos Proto Oncogene Proteins,p55 c fos

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