Objectives High-salt intake has been demonstrated in link to hypertension, and cardiovascular diseases could be programmed in fetal origins. We determined the influence of high-salt diet during pregnancy on the development of the heart. Methods Fetal cardiac structures, cell cycle, renin–angiotensin system (RAS), and epigenetic alternations in the heart following maternal high salt intake during pregnancy were examined. Results Following exposure to high salt, disorganized myofibrillae and mitochondria cristae loss were found in the fetus, S-phase for cardiac cells was enhanced, plasma angiotensin II decreased, and cardiac angiotensin II increased in the fetus. Angiotensin II-increased S-phase in the fetal cardiac cells was primarily via AT1 receptor mechanisms. AT2 receptor mRNA and protein in the fetal heart were not affected, whereas AT1 receptor protein, AT1a, and AT1b mRNA were increased. DNA methylation was found at the CpG sites that were related to AT1b receptors in the fetal heart. Cardiac AT1 receptor protein in the adult offspring was also higher following exposure to prenatal high salt. Conclusion The results suggest a relationship between high-salt diet in pregnancy and developmental changes of the cardiac cells and renin–angiotensin system.

Angiotensin-converting enzyme (ACE) is a major target in the treatment of cardiovascular diseases (CVDs). In addition to ACE, ACE2 -which is a homolog of ACE and promotes the degradation of angiotensin II (AngII) to Ang (1-7) -has been recognized recently as a potential therapeutic target in the management of CVDs. This article reviews different metabolic pathways of ACE and ACE2 (AngI-AngII-AT1 receptors and AngI-Ang (1-7)-Mas receptors) in the regulation of cardiovascular function and their potential in new drug development in the therapy of CVDs. In addition, recent progress in the study of angiotensin and ACE in fetal origins of cardiovascular disease, which might present an interesting field in perinatal medicine and preventive medicine, is briefly summarized.

Previous studies have suggested that prenatal exposure to nicotine is associated with abnormal development in fetuses, including fetal brain damage. The present study determined the effect of maternal administration of nicotine during different gestational periods on brain nicotine receptor subunits in fetal rats. Subcutaneous injections of nicotine in maternal rats from the early and middle gestation decreased fetal blood PO 2 , increased fetal blood PCO 2 and hemoglobin, and decreased fetal brain weight. The nicotinic acetylcholine receptor (nAChRs) mRNA abundance in the fetal brain was significantly changed by prenatal treatment with nicotine during pregnancy. Fetal α2, α4, α7, and β2 units were significantly increased in the brain by prenatal exposure to nicotine in rat fetuses. However, the expression of mRNA of fetal brain α3, α5, β3, and β4 units were not changed. The results showed that prenatal nicotine can change the development of both α and β subunits of nAChRs in the fetal brain at gene level in association with restriction of fetal brain growth and in utero hypoxia.

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Hypoxia-affected fetal renal development was associated with renal apoptosis and Beclin 1 signaling-mediated autophagy.

Aims-Maternal cigarette smoking accompanied with fetal and neonatal growth restriction causes abnormalities in organ development in the postnatal life. The present study determined the effect of maternal administration of nicotine on the development of the kidney in rats by examining the expression of renal angiotensin II receptors at mRNA and protein levels as well as kidney weight during postnatal development.Methods-Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation and up to 10 days after delivery. Kidneys were removed and collected from both male and female offspring at ages of 14-day-old, 30-day-old, and 5-month-old. Maternal nicotine administration significantly reduced renal AT 2 receptor (AT 2 R) mRNA and protein abundance in both males and females at all three developmental ages examined.Results-Although AT 1 receptor (AT 1 R) mRNA and protein levels were not significantly changed between the control offspring and the offspring exposed to maternal nicotine during the early developmental period, the renal AT 1 R/AT 2 R ratio was significantly increased. This was associated with a significant decrease of kidney weight in both male and female offspring. Conclusions-The results demonstrated that the development of renal angiotensin II receptor could be changed following exposure to perinatal nicotine, and such change in the kidney could be long-term in postnatal life.

Objective Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Current research has focused on endothelial dysfunction regarding pathogenesis of preeclampsia. However, very limited or no studies so far have been performed to assess possible damaged endothelial cell growth/development in the placenta–umbilical cord circulation system in human preeclampsia. Methods We isolated and cultured human umbilical cord vein endothelial cells (HUVECs) from normal and preeclampsia pregnancies in vitro. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to measure cell growth and flow cytometric analysis to determine cell-cycle distribution. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was employed for cell apoptosis experiments. Results The study showed that the cell growth was significantly suppressed, accompanied by the increased G1 arrest and apoptosis in cultured HUVECs from preeclampsia pregnancies comparing with normotensive controls. Protein P53 was upregulated in the cultured HUVECs from preeclampsia pregnancies, which induced G1 arrest, followed by upregulating P21 expression, and downregulating cyclin E expression and CDK2–cyclin E complexes. On the other hand, upregulation of P53 also activated Bax gene and repressed Bcl-2 and BIRC5 genes, resulting in an increase of the Bax/Bcl-2 ratio and subsequently activating caspase cascade, ultimately led to an initiation of the apoptotic machinery. Conclusion These results indicated that in preeclampsia, vascular endothelial cells could be damaged and cellular proliferation was depressed in human placenta–umbilical cord circulation, adding new information on endothelial cell injury for better understanding the pathogenesis of preeclampsia.