Relationship Between The Expression Of Ace2and Hypertension In Wky And Shr

Rennin-angiotensin system (RAS) plays a major role in regulating blood pressure and blood volume, maintaining the balance of fluid and electrolyte, promoting cell growth. Angiotensin converting enzyme2(ACE2) is a new factor of RAS which extensively involved in the occurrence and development of many diseases such as hypertension, heart failure, diabetes, SARS, liver injury and so on. Therefore, ACE2has been paid attention to many researchers as disease markers and new targets for drug therapy. However, the mechanisms of ACE2in these physiological and pathological processes have still not been cleared. In this study we selected Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) as experimental animals and revealed the expression of ACE2and other key fators of RAS in heart, kidney, Hypothalamus and pituitary from WKY and SHR. We also will explore its effects among blood pressure. The research consists of two parts:1ACE, ACE2Expression Difference of Heart and Kidney between WKY and SHR and Relationship with HypertensionObjective The purpose of this work is to investigate the effects of ACE and ACE2on the pathogenesis of hypertension in SHR rats by comparing the difference of ACE and ACE2expression in heart and kidney between WKY and SHR rats. Methods8male WKY rats and8male SHR rats which were about300g of weight and14-week-olds, were entrained to free access to food and tap water for one week. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart period (HP) of all experimental rats were recorded by BSN-II Multi-channel non-invasive pressure measurement system. After weighed, All16rats were killed, and plasma, heart and kidney tissues of these rats were immediately collected. The contents of AngII in plasma were detected by RIA, the mRNA expression of ACE, AT1R, ACE2and MasR in heart and kidney were analyzed by Real-time PCR, and the expression level of ACE2protein in heart and kidney were measured by Western blot. Results The results showed that SBP, SDP of SHR were obviously higher than that of WKY (138.72±4.97VS191.75±4.06, P<0.01;101.68±3.96VS140.67±4.39,P<0.01),but there were no significant differences of HR and BW between two groups (P>0.05);The content of AngII in plasma of SHR were raised sharply compared with WKY (1.99±0.09 VS2.60±0.08, P<0.05). Comparison with WKY, the expression of ACE mRNA in heart and kidney from SHR were significantly increased (P<0.05), while the expression of ACE2mRNA and protein in heart and kidney were significantly decreased (P<0.05); the expression of AT1R and MasR mRNA both heart and kidney from SHR had a little variance compared with that of WKY (P>0.05). Conclusion1) These datas indicated that the imbalance of the expression of ACE and ACE2may be an importance reason resulted in hypertension of SHR rats. It is very possible that the ACE-Angll-ATIR axis was over-activity in local RAS, while ACE2-Ang(1-7)-MasR axis was relatively insufficient.2) We also indicate the abnormal expression of ACE and ACE2may be related to genetic background.2ACE, ACE2Expression Difference of Hypothalamus and Pituitary between WKY and SHR and Relationship with HypertensionObjective Our previous research has demonstrated that the expression of ACE2in heart and kidney were different between WKY and SHR, but reports about ACE2in hypothalamus and pituitary have not cleared yet. Therefore, In this work we will investigate mRNA and protein expression of ACE2in hypothalamus and pituitary from WKY and SHR, as well as their relationship with hypothalamus-Pituitary-adrenal axis. Methods8male WKY rats and8male SHR rats which were about300g of weight and14-week-olds, were entrained to free access to food and tap water for one week. Then all experimental rats were killed, and plasma, hypothalamus and pituitary of these rats were collected immediately.(1)The contents of CRH、ACTH. Ald and AngⅡ in plasma were detected by RIA.(2)The mRNA expression of ACE, AT1R, ACE2and MasR in hypothalamus and pituitary were analyzed by Real-time PCR.(3) The expression level of ACE2protein in hypothalamus was measured by Western blot. Results The contents of CRH, ACTH and Ald in plasma of SHR were decreased by84%,31%,35%compared with WKY (P＜0.05), but the contents of Angll in plasma was increased by31%(P<0.05). Compared with the WKY, the expression of ACE mRNA in hypothalamus from SHR were significantly increased (P＜0.05), while the expression of ACE2mRNA and protein in hypothalamus were decreased (0.05<P<0.1); Meanwhile, ACE/ACE2ratio increased significantly (P＜0.05). However, the expression of ACE and ACE2in pituitary and the expression of AT1R and MasR mRNA both in hypothalamus and pituitary from SHR had a little variance compared with that of WKY (P>0.05). Conclusion (1) These results demonstrate for the first time that ACE2is constitutive expressed in hypothalamus and pituitary from rats.(2) RAS plays an important role during blood pressure.