The Effect Of Maternal High Salt In The Offsprings Hypternsion Programming

Background:Hypertension is a common cardiovascular disease.The origin and biological mechanisms of fetal programming has attracted attention.The 'foetal origins of adult disease' hypothesis is important to preventative medicine.Epidemiological studies have indicated that susceptibility of hypertension and cardiovascular diseases may result from high salt diet.The mechanisms underlying programming are likely to be multifactorial.However,further studies have shown that programming of hypertension may occur in fetal origins and related to changes of the renin angiotensin systemPurpose:The present study was proposed:1.To explore the development of the fetal RAS following metemal high salt diet.2.To determine the relationship between the fetal RAS and body fluid balance.3.To identify changes in the fetal heart,kidney, and brain induced by meternal high salt diet.4.To determine the effect of intrauterine high salt on the fetal heart and DNA methylation.Method:1.Pregnant rats were randomized to a normal-salt(1%) or high-salt(8%) diet from gestational day(GD) 3 to GD21,there were 8 rats in each group.Rats were placed in metabolic cages,food and water intake,urine volume,and urinary sodium, and maternal and fetal plasma osmolarity,and sodium concentration were measured.2. Transmission electron microscope was used for analysis of the fetal heart and kidney.3. Plasma and tissue Angâ…¡,and aldosterone were measured by radioimmunoassay.4.The component of RAS in the fetal heart,kidney,brain and liver were measured by real time PCR and western blot.5.Cell cycle was estimated for the proliferation of the fetal heart and mesangial cells.6.Pyrosequencing analysis for the DNA methylation of the AT_1b promoter in the fetal heart.Results:1.Water intake,urine volume and urine sodium excretion were increased by high salt diet in pregnant rats.There was no significantly difference in plasma Na⁺ and osmolarity in maternal and fetal rats between normal diet and high salt diet.2. Maternal salt loading elicited ultrastructural changes in the fetal heart and kidney.3. High salt diet caused plasma Angâ…¡and aldosterone concentrations decreased in both mothers and fetuses.Angâ…¡concentration was increased in the fetal myocardium and kidney in high salt diet.4.AT₁ receptor protein was increased in the fetal heat and kidney induced by high salt diet,AT₁,and AT₂ receptor protein were increased in the fetal brain by high salt diet;high salt diet caused the changes in the fetal RAS as following:AT_1a and AT_1b mRNA were increased in the heart,AT_1b mRNA was increased in the kidney,AT_1a,AT_1b,and AT₂ mRNA were increased the brain,angiotensinogen mRNA was increased in the liver and dereased in the brain.5.Angâ…¡stimulated the fetal heart and mesangial cell proliferation;the effect of Angâ…¡on cellular growth is primarily mediated by the AT₁ receptor.6.DNA hypomethylation of AT_1b promoter resultd from maternal high salt diet.Conclusion 1.Maternal high salt diet had adverse effects on the development of the fetal heart and kidney.2.The local RAS activation induced by maternal high salt diet contributed to the change of the heart and kidney.3.Epigenetic mechanisms contributed to the prenatal programming of hypertension by maternal high salt diet.