Effects Of Benazepril And Valsartan On ACE2 Expression In Heart, Kidney, Thorax Aorta Of Spontaneously Hypertensive Rats

【Objective】 To investigate the effects of benazepril and valsartan on ACE2 expression in heart, kidney, thorax aorta of spontaneously hypertensive rats(SHR) and to explore the possible mechanism of ACE2 in the pathogenesis of hypertension. 【Methods】(1) 28 12-week-old male SHR were allocated to four groups at random as followed (7 rats in each group): a. placebo control(distilled water ig.) (SHRc) b. benazepril (10mg/kg/d ig.)(SHRb) c. small-dose valsartan (10mg/kg/d ig.)(SHRsv) d. large-dose valsartan (30mg/kg/d ig.)(SHRlv). 7 age and weight matched male normotensive WKY rats were set as normal control. Treatment lasted three months. Blood pressure and weight of SHR were measured once a month. Rats were killed after 3 months' therapy and then measured the weights of the whole heart and left ventricle, which were used to calculate the ratio of the heart weight to body weight(H/B) and the left ventricle mass index(LVMI). (2) Generally embeded the heart, kidney, thorax aorta and the third-grade branch of mesentery artery of rats with paraffin. HE pigmentized the slices of thorax aorta and the third-grade branch of mesentery artery and then calculated the ratio of the lumen to the wall of these vessels(L/W). Stained the collagen in the slice of the heart by sirius red to observe the effects of the drugs on vessel remodeling and myocardial fibrosis. Compared ACE2 expression level in kidney among groups by immunohistochemistry. (3) Took rats' left ventricle, left kidney and thorax aorta as samples and then compared the expression levels of ACE and ACE2 mRNA in these samples among all groups. (4) Cultured vascular smooth muscle cells(VSMC) of SHR and WKY rats in vitro and to observe the expression levels of ACE and ACE2 mRNA in VSMC derived from these two strains.【Results】 Benazepril and valsartan treatment obviously decreased the blood pressure, H/B and LVMI of SHR, especially SHRlv (p<0.05). (2) Compared with the WKY rats control, the content of collagen in the heart of SHRc was obviously increased , while L/W was significantly decreased(p<0.05). Benazepril and valsartan treatment obviously decreased the content of collagen in the heart, especially SHRlv. There was an increase trend of L/W in all groups with the intervention of drugs. However, only SHRlv significantly increased L/W of both the thorax aorta and the third-grade branch of mesentery artery(p<0.05, both). SHRsv only significantly increased L/W of the thorax aorta(p<0.05) and the difference between SHRb and SHRc did not reached the statistical significance(p>0.05). (3) The density and the area of ACE2 immunostaining in kidney of all SHR groups were significantly decreased while compared with WKY rats. Benazepril treatment had no significant effect on expression of ACE2 in kidney of SHR while valsartan intervention obviously increased its expression level, especially SHRlv. (4) Expression of ACE2 mRNA in heart, kidney, thorax aorta of SHR were obviously decreased when compared with WKY rats while the expression of ACE mRNA were obviously increased (p<0.05). (5) After three months' intervention of valsartan, the expression levels of ACE2 mRNA were notably increased in the heart, kidney, thorax aorta of SHR while compared with SHRc, which was more signicant in SHRlv than SHRsv(p<0.05). There was no significant change of ACE2 mRNA expression level in SHRb(p>0.05). (6) Expression level of ACE2 mRNA was significantly lower than ACE mRNA in cultured VSMC. ACE mRNA expression level was significantly higher in VSMC derived from SHR than VSMC derived from WKY rats(p<0.05), while ACE2 mRNA expression level was significantly lower in VSMC from SHR when compared with WKY rats(p<0.05).【Conclusions】(1) Benazepril and valsartan treatment may obviously decrease the blood pressure of SHR and relieve left ventricular hypertrophy. Valsartan can obviously improve the structure of vessels of SHR and these effects of valsartan is in a dose-dependent manner. (2) Expression level of ACE2 mRNA is significantly lower in the heart, kidney, thorax aorta an...