Blockade of angiotensin-converting enzyme or tumor necrosis factor-α reverses maternal high-fat diet-induced sensitization of angiotensin II hypertension in male rat offspring

Xue-Fang Wang; Jian-Dong Li; Yan-Li Huo; Yu-Ping Zhang; Zhi-Qin Fang; Hai-Ping Wang; Wei Peng; Alan Kim Johnson; Baojian Xue

doi:10.1152/AJPREGU.00200.2019

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Blockade of angiotensin-converting enzyme or tumor necrosis factor-α reverses maternal high-fat diet-induced sensitization of angiotensin II hypertension in male rat offspring

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Blockade of angiotensin-converting enzyme or tumor necrosis factor-α reverses maternal high-fat diet-induced sensitization of angiotensin II hypertension in male rat offspring

Xue-Fang Wang, Jian-Dong Li, Yan-Li Huo, Yu-Ping Zhang, Zhi-Qin Fang, Hai-Ping Wang, Wei Peng, Alan Kim Johnson and Baojian Xue

American journal of physiology. Regulatory, integrative and comparative physiology, Vol.318(2), pp.R351-R359

02/01/2020

DOI: 10.1152/AJPREGU.00200.2019

PMCID: PMC7052597

PMID: 31746626

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Abstract

Maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular diseases in adult offspring. Our previous study demonstrated that maternal HFD enhances pressor responses to ANG II or a proinflammatory cytokine (PIC), which is associated with increased expression of brain renin-angiotensin system (RAS) components and PICs in adult offspring. The present study further investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) blocks sensitization of ANG II hypertension in offspring of HFD dams. All offspring were bred from dams with normal fat diet (NFD) or HFD starting two weeks before mating and maintained until weaning of the offspring. Then the weaned offspring were treated with an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water through the end of testing with a slow-pressor dose of ANG II. RT-PCR analyses of the lamina terminalis and paraventricular nucleus revealed upregulation of mRNA expression of several RAS components and PICs in male offspring of HFD dams when compared with age-matched offspring of NFD dams. The enhanced gene expression was attenuated by blockade of either RAS or PICs. Likewise, ANG II administration produced an augmented pressor response in offspring of HFD dams. This was abolished by either ACE or TNF-α inhibitor. Taken together, this study provides mechanistic evidence and a therapeutic strategy that systemic inhibition of the RAS and PICs can block maternal HFD-induced sensitization of ANG II hypertension, which is associated with attenuation of brain RAS and PIC expression in offspring.

Angiotensin II

Angiotensin-Converting Enzyme Inhibitors - pharmacology

Animal Nutritional Physiological Phenomena

Animals

Antihypertensive Agents - pharmacology

Blood Pressure - drug effects

Brain - drug effects

Brain - metabolism

Brain - physiopathology

Captopril - pharmacology

Diet, High-Fat

Disease Models, Animal

Female

Hypertension - chemically induced

Hypertension - metabolism

Hypertension - physiopathology

Hypertension - prevention & control

Male

Maternal Nutritional Physiological Phenomena

Pentoxifylline - pharmacology

Pregnancy

Prenatal Exposure Delayed Effects

Rats, Sprague-Dawley

Renin-Angiotensin System - drug effects

Tumor Necrosis Factor Inhibitors - pharmacology

Details

Title: Subtitle: Blockade of angiotensin-converting enzyme or tumor necrosis factor-α reverses maternal high-fat diet-induced sensitization of angiotensin II hypertension in male rat offspring
Creators: Xue-Fang Wang - Life Science Research Center, Hebei North University, Zhangjiakou City, China
Jian-Dong Li - Life Science Research Center, Hebei North University, Zhangjiakou City, China
Yan-Li Huo - Life Science Research Center, Hebei North University, Zhangjiakou City, China
Yu-Ping Zhang - Life Science Research Center, Hebei North University, Zhangjiakou City, China
Zhi-Qin Fang - First Affiliated Hospital, Hebei North University, Zhangjiakou City, China
Hai-Ping Wang - Life Science Research Center, Hebei North University, Zhangjiakou City, China
Wei Peng - Life Science Research Center, Hebei North University, Zhangjiakou City, China
Alan Kim Johnson - Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa
Baojian Xue - Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa
Resource Type: Journal article
Publication Details: American journal of physiology. Regulatory, integrative and comparative physiology, Vol.318(2), pp.R351-R359
DOI: 10.1152/AJPREGU.00200.2019
PMID: 31746626
PMCID: PMC7052597
NLM abbreviation: Am J Physiol Regul Integr Comp Physiol
ISSN: 0363-6119
eISSN: 1522-1490
Grant note: P01 HL014388 / NHLBI NIH HHS R01 HL139575 / NHLBI NIH HHS
Language: English
Date published: 02/01/2020
Academic Unit: Psychological and Brain Sciences; Neuroscience and Pharmacology; Neurology (Pediatrics); Health, Sport, and Human Physiology
Record Identifier: 9984213427602771

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