Effects of Benazepril and Valsartan on ACE2 Expression in Kidney of SHR

ObjectiveTo investigate the effects of benazepril and valsartan on plasma Ang Ⅱ and ACE2 expression in kidney of spontaneously hypertensive rats(SHR) and the role of ACE2 in the pathogenesis of hypertension. Methods Four groups of 12-week-old male SHR were studied with 7 rats in each group: placebo control (Sc), benazepril (10 mg/kg·d)(Sb), low-dose valsartan (10 mg/kg·d)(Sl) and high-dose valsartan (30 mg/kg·d )(Sh). 7 male normotensive WKY rats were served as normal control. Drug therapy was administered for 3 months. Plasma Ang Ⅱ was measured by RIA. ACE and ACE2 mRNA in kidney were determined by RT-PCR and the expression level of ACE2 protein in kidney was measured by immunohistochemistry. Results The expression level of ACE2 mRNA and protein in kidney of SHR was significantly lower than WKY rats, while the level of and ACE mRNA in kidney was significantly higher(P0.05). Valsartan treatment obviously lowered the blood pressure of SHR and increased plasma Ang Ⅱ. The expression level of ACE2 (mRNA and protein)in kidney was increased by valsartan in a dose-dependent manner (P0.05). However, benazepril had little effect on plasma Ang Ⅱ and ACE2 mRNA expression in kidney. ConclusionThe imbalance between ACE and ACE2 may play an important role in the mechanism of hypertension in SHR. The facts that angiotensin receptor blocker(ARB) increases plasma Ang Ⅱ and tissue ACE2 expression may be speculated as novel pharmacological mechanism of the anti-hypertensive effect of ARB.