Overuse of salt is common by pregnant women due to physiological and pathophysiological changes during pregnancy. A strong relationship between high salt diet and increased blood pressure (BP) has been demonstrated. Although a number of studies have demonstrated that angiotensin II (ANG II) and its receptors play an important role in salt intake and BP controlling in adults, there is very limited information on the effects of maternal high salt ingestion on the development of fetal swallowing behavior, ANG receptor subtypes-AT1?R and AT2-R, and vascular homeostasis, as well as long-term programming influence on cardiovascular regulation in the offspring. Notably, our preliminary studies have demonstrated the importance of the in utero environmental (e.g., osmotic change) and hormonal (e.g., ANG II) factors on the fetal development of osmoregulatary and neurochemical mechanisms for body fluid and cardiovascular regulation. In light of these, this application hypothesizes: 1) Maternal salt intake during pregnancy may affect AT1-R / AT2-R that are important to body fluid balance and vascular contractility before and after birth;2) The RAS may play a role in cardiovascular remodeling in the fetus and offspring under conditions of high salt loading during pregnancy;3) The RAS also may play a critical role in the development and programming of salt appetite under conditions of maternal high salt intake during pregnancy. Therefore, the proposed studies will determine the effects of maternal salt loading on AT1-R and AT2-R and vascular contractility in prenatal and postnatal life, and determine the RAS- mediated cardiovascular changes in the fetus and offspring to maternal salt loading during pregnancy, as well as determine the effect of AT1-R / AT2-R agonists on age-dependent swallowing and programmed salt appetite. The data gained will add important information to understanding of influence of maternal high salt in pregnancy on renin-angiotensin system mediated remolding of swallowing behavior, vascular contractility, and salt appetite in developmental origin. Project Narrative: This project will determine the acute effect of maternal salt intake on the fetus in utero, and the chronic influence of maternal salt diet on the offspring's salt appetite and cardiovascular homeostasis. The proposed study postulates that renin-angiotensin system (RAS) mechanisms are functional in behavioral and cardiovascular development prior to birth, and that maternal salt intake may cause imprinting on the offspring. Notably, high hydration is normal in fetuses associated with a preponderance of AT2-R, while low hydration of adults is accompanied by a preponderance of AT1-R. It is of utmost importance to investigate the extent to which there is any link between the development of the ANG receptors and high hydration status in the fetal body, as well as their responses, under conditions of salt loading. The results gained may generate significant information on the shift from predominantly AT2-R to predominantly AT1-R associated with birth-related change in salt and water balance. In addition, in vitro vascular contractility studies will determine the effect of RAS mechanisms involved in vascular regulation related to salt loading in fetal and offspring tissues at various ages. Together, the focused and integrated approaches of this project will yield important information in preventive medicine, regarding the development of the RAS controlling that is critical for fluid volume and cardiovascular homeostasis, and acute and chronic effects of maternal salt intake on the fetus in utero, and possibly on the imprinting in the offspring.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-EMNR-H (02))
Program Officer
Mitchell, Megan S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Loma Linda University
Other Basic Sciences
Schools of Medicine
Loma Linda
United States
Zip Code
Mao, Caiping; Liu, Rong; Bo, Le et al. (2013) High-salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system. J Endocrinol 218:61-73
Shi, Lijun; Mao, Caiping; Zeng, Fanxing et al. (2012) Central angiotensin I increases swallowing activity and oxytocin release in the near-term ovine fetus. Neuroendocrinology 95:248-56
Wu, Lei; Mao, Caiping; Liu, Yujuan et al. (2011) Altered dipsogenic responses and expression of angiotensin receptors in the offspring exposed to prenatal high sucrose. Peptides 32:104-11
Zhang, Huiying; Fan, Yisun; Xia, Fei et al. (2011) Prenatal water deprivation alters brain angiotensin system and dipsogenic changes in the offspring. Brain Res 1382:128-36
Mao, Caiping; Hou, Jianquan; Ge, Jianyi et al. (2010) Changes of renal AT1/AT2 receptors and structures in ovine fetuses following exposure to long-term hypoxia. Am J Nephrol 31:141-50
Xu, F; Mao, C; Ding, Y et al. (2010) Molecular and enzymatic profiles of mammalian DNA methyltransferases: structures and targets for drugs. Curr Med Chem 17:4052-71
Shi, Lijun; Mao, Caiping; Xu, Zhice et al. (2010) Angiotensin-converting enzymes and drug discovery in cardiovascular diseases. Drug Discov Today 15:332-41
Yang, Weili; Mao, Caiping; Xia, Fei et al. (2010) Changed salt appetite and central angiotensin II-induced cellular activation in rat offspring following hypoxia during fetal stages. Peptides 31:1177-83
Shi, Lijun; Mao, Caiping; Zeng, Fanxing et al. (2010) Central angiotensin I increases fetal AVP neuron activity and pressor responses. Am J Physiol Endocrinol Metab 298:E1274-82
Ding, Yang; Lv, Juanxiu; Mao, Caiping et al. (2010) High-salt diet during pregnancy and angiotensin-related cardiac changes. J Hypertens 28:1290-7

Showing the most recent 10 out of 12 publications