The Influence Of Renin-angiotensin Blockers Given During Pregnancy On The Cardiac Structure And Artery In Offspring Rats

ObjectiveTo study the influence of renin-angiotensin blockers given during pregnantstages on the structural and functional changes of heart and artery in adult offspringrats.MethodsSpontaneously hypertensive rats were fed with captopril or losartan throughoutpregnancy and or weaning, whose offspring were fed with captopril or with losartanentil16weeks old. Blood pressure, left ventricular mass index, wall to lumen arearatios(WPL) of mesenteric artery(3rd grade branch), endothelium-dependentvasodilation and endothelium-independent vasodilation of thoracic aorta andmesenteric artery(3rd grade branch) were determined in8and16-week-old offspringof captopril treated SHR or losartan treated SHR, which raised with captopril(F1CF1C)or with losartan(F1LF1L). The same detection indicators above were determined in8and16-week-old offspring of captopril treated SHR or losartan treated SHR whichwere raised without captopril (F1CF1N) or without losartan (F1LF1N) and in offspring ofSHR raised with captopril(F1NF1C) or with losartan(F1NF1L). The mRNA expression ofAT1gene and ATRAP gene in heart were detected in each group at8and16weeksold by QRT-PCR. DNA methylation was also detected by pyrosequencing. Theprotein expression of AT1and ATRAP in the male offsprings’ heart were detected ineach group by western blot. The immortalized cardiomyocyte cell line H9c2whichexpresses endogenous AT1and ATRAP was cultured with angiotensin II (100nmol/l)and10-9-10-5mmol/l captopril or losartan. The mRNA expression of AT1b gene andATRAP gene were detected in H9c2cell by QRT-PCR. DNA methylation wasdetected also by pyrosequencing. The protein expression of AT1and ATRAP weredetected in H9c2cell by western blot.Result1.F1CF1N, F1NF1C, F1CF1C,F1LF1N,F1NF1L, F1LF1Loffspring rats had lower blood pressure（P<0.01）, lower left ventricular weight index（P<0.01）, lower WPL（P<0.01）, higher endothelium-dependent vasodilation（P<0.01） and higherendothelium-independent vasodilation（P<0.01）.2.AT1b mRNA and AT1protein of heart were lower in F1CF1N, F1NF1C, F1CF1C（P<0.01）,F1LF1N,F1NF1Land F1LF1L（P<0.01）at8weeks old.AT1b mRNA andAT1protein of heart were lower in F1NF1C, F1CF1C,F1NF1Land F1LF1L（P<0.01）at16weeks old. ATRAP mRNA and ATRAP of heart were higher in F1CF1N, F1NF1C, F1CF1C,F1LF1N,F1NF1L,F1LF1L（P<0.01）at8and16weeks old.3.DNA methylation of ATRAP gene was decreased in F1CF1N, F1NF1C, F1CF1C,F1LF1N,F1NF1Land F1LF1L（P<0.01）.4.10-9-10-5mmol/l captopril and losartan decreased AT1b mRNA（P<0.01） andthe protein expression of AT1（P<0.01） in H9c2cell.10-9-10-5mmol/l captopril andlosartan increased ATRAP mRNA（P<0.01）and ATRAP（P<0.01）in H9c2cell.5.10-9-10-5mmol/l captopril and losartan decreased DNA methylation of ATRAPgene in H9c2cell（P<0.01）.Conclusion1. The treatment which parental SHR feed captopril or losartan andprehypertension treatment could improve blood pressure of SHR offspring. Structureand function of heart and artery were improved also by parental treatment.2. The treatment which parental SHR feed captopril or losartan andprehypertension treatment could improve endothelium-dependent vasodilation andendothelium-independent vasodilation of offsprings’ thoracic aorta and mesentericartery(3rd grade branch).3. The profit of structure and function of heart and artery might associate withAT1b and ATRAP.4. DNA methylation of ATRAP gene might associate with the mRNA and proteinexpression of ATRAP.5. Internal environment of perinatal had tremendous impact on the formation ofblood pressure and functional changes of cardiovascular system.