The Influence Of Hypoxia During Different Pregnant Stages On The Cardiac Structure And Tissue RAS In Adult Offspring Rats

Objective To study the influence of hypoxia during different pregnant stages on the myocardial remodeling and cardiac RAS in adult male offspring.Methods 24 pregnant rats were randomly assigned to four groups as follows: hypoxia group started in early pregnancy (from day 3 to day 21 of pregnancy), hypoxia group started in mid-pregnancy (from day 9 to day 21 of pregnancy), hypoxia group started in late pregnancy (from day 15 to day 21 of pregnancy), and control group. Each group contained 6 animals. The left ventricular weight index, the diameter of myocardial fibre, the mRNA and protein expression of collagenâ… and collagenâ…¢, the expression of ACE-Angâ…¡-AT₁ axis and ACE2-Ang-(1-7)-Mas axis in the left ventricle of male offspring rats at 3 months and 5 months of age were detected in each group.Results Hypoxia started in early or middle stage of pregnancy increased the mRNA and protein expression of collagenâ… and collagenâ…¢in the left ventricle of male offspring rats, but without hypertrophic myocardial cells, and the cardiac collagen deposition was independent of the changes of blood pressure. Hypoxia during pregnancy could activate the cardiac ACE-Angâ…¡-AT₁ axis in adult male offspring by changing the mRNA and protein expression of AT₁ receptors, the protein expression of ACE or the generation of Angâ…¡(all P<0.05), and then influenced the downstream MAP/ERK signaling pathway, which was obvious in the hypoxic group started in mid-pregnancy. Hypoxia during pregnancy could inhibit the cardiac ACE2-Ang-(1-7)-Mas axis in adult male offspring by reducing the mRNA and protein expression of Mas receptors, the protein expression of ACE2 or the generation of Ang-(1-7)(all P<0.05), which was also obvious in the hypoxic group started in mid-pregnancy.Conclusions Hypoxia during pregnancy could lead to the the cardiac collagen deposition in adult male offspring, and program the cardiac ACE-Angâ…¡-AT₁ axis and ACE2-Ang-(1-7)-Mas axis. The change of the balance relationship between the two axises will influence the total effect of cardiac RAS and lead to the cardiac phenotype changes in offspring. All these changes are most obviously observed in the adult male offspring rats of hypoxia group started in mid-pregnancy, which indicates that the evident changes of internal environment around the critical period for the development of fetal cardiovascular development may have more obvious effects on cardiac structure in offspring rats.