High sucrose intake during gestation increases angiotensin II type 1 receptor-mediated vascular contractility associated with epigenetic alterations in aged offspring rats.
Accruing evidence have confirmed that the fetal programming in response to adverse environmental in utero factors plays essential roles in the pathogenesis of hypertension in later life. High sugar intake has been accepted worldwide in everyday life diet and becomes the critical public health issue. Our previous studies indicated that intake of high sucrose (HS) during pregnancy could change the vascular reactivity and dipsogenic behavior closely associated with abnormal renin-angiotensin system (RAS), to increase the risk of hypertension in adult offspring. In the present study, we tested the hypothesis that maternal HS intake in pregnancy may further deteriorate the Ang II-induced cardiovascular responses in the aged offspring. HS intake was provided to pregnant rats throughout the gestation. Blood pressure (BP) in conscious state and vascular contractility in vitro were measured in 22-month-old aged offspring rats. In addition, mRNA and protein expressions and epigenetic changes of Ang II type 1 receptor (AT1R) gene in blood vessels were determined with the methods of real-time RT-PCR, Western blotting, and Chromatin Immunoprecipitation Assay (CHIP). Results showed that, in the aged offspring, maternal HS intake during gestation would cause the elevation of basal BP which could be diminished by losartan. Although the circulatory Ang II was not changed, levels of local Ang II were significantly increased in blood vessels. In addition, prenatal HS exposure would significantly enhance the AT1R-mediated vasoconstrictions in both aorta and mesenteric arteries of the aged offspring. Moreover, in the aged offspring of prenatal HS exposure, mRNA and protein expressions of AT1R gene in both large and small blood vessels were significantly increased, which should be closely associated with the changes of epigenetic mechanisms such as histone modifications. Collectively, we proposed that maternal HS intake during gestation would cause abnormal BP responses mediated via the enhancement of vascular RAS, together with the increased expression of AT1R gene related to the its epigenetic changes, which would actually lead to the overt phenotype of hypertension in the aged offspring.
Institute for Fetology and Reproductive Medicine Center, First Hospital of Soochow University, Suzhou, 215006, China; Suzhou Industrial Park Centers for Disease Control and Prevention, Suzhou, China.
Lei
L
Wu
Institute for Fetology and Reproductive Medicine Center, First Hospital of Soochow University, Suzhou, 215006, China; Zhangjiagang Centers for Disease Control and Prevention, Suzhou, China.
Aiping
A
Shi
Institute for Fetology and Reproductive Medicine Center, First Hospital of Soochow University, Suzhou, 215006, China.
Di
D
Zhu
Institute for Fetology and Reproductive Medicine Center, First Hospital of Soochow University, Suzhou, 215006, China.
Le
L
Bo
Institute for Fetology and Reproductive Medicine Center, First Hospital of Soochow University, Suzhou, 215006, China.
Yuan
Y
Zhong
Institute for Fetology and Reproductive Medicine Center, First Hospital of Soochow University, Suzhou, 215006, China.
Juan
J
Wang
Institute for Fetology and Reproductive Medicine Center, First Hospital of Soochow University, Suzhou, 215006, China.
Zhice
Z
Xu
Institute for Fetology and Reproductive Medicine Center, First Hospital of Soochow University, Suzhou, 215006, China. Electronic address: maocp1018@163.com.
Caiping
C
Mao
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D047109:Fetal Development; D006657:Histones / Q000378:metabolism; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D013395:Sucrose / Q000633:toxicity*; D035181:TATA-Box Binding Protein / Q000378:metabolism; D059467:Transcriptome; D014661:Vasoconstriction
D006657:Histones; D044140:Receptor, Angiotensin, Type 1; D035181:TATA-Box Binding Protein; D000804:Angiotensin II; D013395:Sucrose
Aged offspring; Angiotensin; Epigenetics; High sucrose; Hypertension