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Prenatal cold exposure causes hypertension in offspring by hyperactivity of the sympathetic nervous system.

Authors
  • Chen, Ken1, 2, 3
  • Sun, Dongdong2, 3
  • Qu, Shuang2, 3
  • Chen, Yue2, 3
  • Wang, Jialiang2, 3
  • Zhou, Lin2, 3
  • Jose, Pedro A4
  • Yang, Yongjian5
  • Zeng, Chunyu6, 3
  • 1 Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P.R. China. , (China)
  • 2 Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, P.R. China. , (China)
  • 3 Chongqing Institute of Cardiology, Chongqing 400042, P.R. China. , (China)
  • 4 Division of Renal Diseases & Hypertension, Departments of Medicine and Pharmacology/Physiology, The George Washington University School of Medicine and Health Sciences, Washington DC, U.S.A.
  • 5 Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P.R. China [email protected] [email protected] , (China)
  • 6 Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, P.R. China [email protected] [email protected] , (China)
Type
Published Article
Journal
Clinical Science
Publisher
Portland Press
Publication Date
May 31, 2019
Volume
133
Issue
9
Pages
1097–1113
Identifiers
DOI: 10.1042/CS20190254
PMID: 31015358
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Environmental temperature plays a role in the variation of blood pressure. Maternal cold stress could affect the physiological phenotype of the offspring, including blood pressure elevation. In the present study, we found that adult offspring of dams exposed to cold have increased systolic and diastolic blood pressure, and decreased urine volume and sodium excretion, accompanied by increased heart rate and heart rate variability, secondary to increased activity of the sympathetic nervous system. Renal denervation or adrenergic receptor blockade decreased blood pressure and increased sodium excretion. The increase in peripheral sympathetic nerve activity can be ascribed to the central nervous system because administration of clonidine, a centrally acting α2 adrenergic receptor agonist, lowered blood pressure to a greater degree in the prenatal cold-exposed than control offspring. Moreover, these prenatal cold-exposed offspring had hypothalamic paraventricular nucleus (PVN) disorder because magnetic resonance spectroscopy showed decreased N-acetylaspartate and increased choline and creatine ratios in the PVN. Additional studies found that prenatal cold exposure impaired the balance between inhibitory and excitatory neurons. This led to PVN overactivation that was related to enhanced PVN-angiotensin II type 1 (AT1) receptor expression and function. Microinjection of the AT1 receptor antagonist losartan in the PVN lowered blood pressure to a greater extent in prenatal cold-exposed that control offspring. The present study provides evidence for overactive peripheral and central sympathetic nervous systems in the pathogenesis of prenatal cold-induced hypertension. Central AT1 receptor blockade in the PVN may be a key step for treatment of this type hypertension. © 2019 The Author(s).

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