| Objective: To study the effect of early over-nutrition on blood pressure and local renin-angiotensin system(RAS) in later life, thereby investigate the change to circulation and local tissue(renal or vascular) RAS by early nutrition and the role on hypertension programming.Methods:(1) Pregnant Sprague-Dawley rats were fed with high-fat diet or standard diet during gestational and lactation period until pups weaned. Thus their offspring were divided into two groups. The high-fat diet group(HF) and the control diet group(Con). Chosing female offspring as study object.(2) Body weight and food intake was monitored once a week throughout life. Systolic blood pressure and heart rate was recorded at the 3th week(3w), 8w and 16 w.(3)Glucose tolerance test of the offspring at the 3w,8w and 16 w were assessed. Triglycerides and cholesterol levels at 3w, 8w and 16 w were measured by enzvmatic assay. Angiotensin â…¡(Angâ…¡) and angiotensin(1-7)(Ang(1-7)) levels at the 3w, 8w and 16 w were measured by ELISA.(4) HE staining was used to observe the morphology of aortic vessel wall at 16 w. The mRNA expression of angiotensin-converting enzyme(ACE), angiotensin converting enzyme 2(ACE2), angiotensin â…¡ type 1 receptor(AT1) and Mas receptor in renal or vascular tissue were determined by Real-time PCR, and the protein expression were determined by Western blot.Results:(1) Body weight was significantly higher in HF group compared to Con group from 1w after birth and persisted into adulthood(except for 9w and 11w). Food energy intake in HF group was significantly higher than Con group in early stage after wean, no difference was found in food energy intake between HF and Con group after 5w.(2) There were no significant differences in systolic blood pressure between HF and Con group at 3w and 8th week(P>0.05), but systolic blood pressure in HF group was significantly higher than Con group at 16w(P<0.05). There were no significant differences in heart rate between HF and Con group at 3w, 8w and 16w(P>0.05).(3) There were no significant differences in serum triglycerides and cholesterol levels between HF and Con group at 3w, 8w and 16w(P>0.05). When given the glucose tolerance test at 3w and 8w, there were no significant differences in blood glucose levels between HF and Con group(P>0.05), but when given it at 16 w, HF group had higher blood glucose levels compared to Con group at 30 and 60min(P<0.05).(4) There were no visible differences in morphology of aortic vessel wall between HF and Con group at 16 th week. There were no significant differences in thickness of aortic vessel wall between HF and Con group at 16w(P>0.05).(5) There were no significant differences in serum Angâ…¡ levels between HF and Con group at 3w, 8w and 16w(P>0.05). There were no significant differences in serum Ang(1-7) levels between HF and Con group at 3w(P>0.05), but serum Ang(1-7) levels of HF group were significantly lower than Con group at 8w and 16w(P<0.05).(6) In renal tissue,there were no significant differences in ACE, ACE2, AT1 and Mas mRNA expression between HF and Con group at 3w(P>0.05). ACE2 mRNA expression of HF group was significantly lower than Con group at 8w and 16w(P<0.05). ACE mRNA expression of HF group was significantly higher than Con group at 8w(P<0.05), and still had higher trend than Con group at 16 w. Mas mRNA expression of HF group was significantly lower than Con group at 8w and 16w(P<0.05). AT1 mRNA expression of HF group was significantly higher than Con group at 8w(P<0.05), but there were no significant differences in AT1 mRNA expression between HF and Con group at 16w(P>0.05). The protein expression of ACE was increased in HF group than Con group at both 8w and 16w(P<0.05), other protein expression were consistent with the mRNA expression.(7) In vascular tissue,there were no significant differences in ACE mRNA expression between HF and Con group at 3w(P>0.05), but ACE mRNA expression was decreased in HF group than Con group at 8w and 16w(P<0.05). There were no significant differences in ACE2, AT1 and Mas mRNA expression between HF and Con group at 3w, 8w and 16w(P>0.05). The protein expression were consistent with the mRNA expression.Conclusion:(1) Early over-nutrition exposure induces higher blood pressure in adulthood. The abnormal expression of RAS, including down-regulation of Ang(1-7) in circulation, up-regulation of ACE and down-regulation of ACE2 and Mas in renal tissue may be the underlying mechanisn.(2) Early over-nutrition induces tissue-specific regulation on vascular and renal RAS. |
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