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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
- Source :
- Am J Physiol Regul Integr Comp Physiol
- Publication Year :
- 2020
- Publisher :
- American Physiological Society, 2020.
-
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.
- Subjects :
- Male
medicine.medical_specialty
Captopril
Physiology
Offspring
Angiotensin-Converting Enzyme Inhibitors
Blood Pressure
030204 cardiovascular system & hematology
Diet, High-Fat
Rats, Sprague-Dawley
Renin-Angiotensin System
03 medical and health sciences
0302 clinical medicine
Pregnancy
Physiology (medical)
Internal medicine
Renin–angiotensin system
medicine
Animals
Pentoxifylline
Antihypertensive Agents
Sensitization
biology
business.industry
Angiotensin II
Brain
Angiotensin-converting enzyme
Maternal Nutritional Physiological Phenomena
medicine.disease
Blockade
Disease Models, Animal
medicine.anatomical_structure
Blood pressure
Endocrinology
Prenatal Exposure Delayed Effects
Hypertension
biology.protein
Animal Nutritional Physiological Phenomena
Female
Tumor Necrosis Factor Inhibitors
Metabolic syndrome
business
hormones, hormone substitutes, and hormone antagonists
030217 neurology & neurosurgery
Research Article
Subjects
Details
- ISSN :
- 15221490 and 03636119
- Volume :
- 318
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Accession number :
- edsair.doi.dedup.....b9b812d54400df27359e39e4c80d3cc6