Effects of enalapril and irbesartan on renal morphology and angiotensin converting enzyme to angiotensin converting enzyme 2 ratio in renovascular hypertensive rat

Objective To observe the effects of enalapril and irbesartan on changes of renal morphology and angiotensin converting enzyme(ACE) and ACE2 ratio in renovascular hypertensive rats(RHR). Methods RHR were induced by Two-kidney-one-clip,at six weeks after operation,rats were randomly divided into RHR group (n=6), enalapril group (n=6) and irbesartan group (n=6), sham-operation rats (n=6) served as negative controls. After six-week treatment, the pathological sections of kidneys were observed through HE staining,the levels of angiotensionⅡ(Ang Ⅱ) and renin activity in kidney tissue and blood plasma were determined with radioimmunoassay;the expressions of ACE2 mRNA and ACE mRNA in kidney tissue were detected by real-time PCR. ResultsCompared with the sham group,blood pressure [(164.4±20.3) vs (115.0±6.8) mm Hg],Ang Ⅱ[(416.3±80.7) vs (285.4±58.4)ng/g pro] and renin activity[(0.69±0.08) vs (0.43±0.08)μg/(g pro·h)](all P0.01) in RHR group weresignificantly increased. Compared with the RHR group,Ang Ⅱ[(234.5±28.3) vs (416.3±80.7) ng/g pro] and renin activity [(0.35±0.07) vs (0.69±0.08)μg/(g pro·h)] in enalapril group were significantly decreased (all P0.01), Ang Ⅱ[(518.1±87.1) vs (416.3±80.7) ng/g pro] and renin activity [(0.87±0.17) vs (0.69±0.08)μg/(g pro·h)] in irbesartan group were significantly increased (all P0.01). The expression of ACE2 mRNA in RHR group kidney was decreased by 47.8% than that in the sham group, ACE mRNA expression was increased by 140.3%, and ACE and ACE2 ratio was increased by 374.2%; compared with the RHR group, ACE2 mRNA expression levels in kidney were increased by 61.4%, ACE mRNA expression and ACE and ACE2 ratio were decreased by 56.3% and 83.7% respectively in irbesartan group (P0.01), ACE mRNA expression levels in kidney and ACE and ACE2 ratio were decreased by 72.8% and 79.6% respectively in enalapril group. With HE staining, the fibrosis, glassy degeneration and thickening of glomerular balloon wall, the thickening, glassy degeneration and luminal stenosis of renal arterioles, renal tubular disorder, protein casts in renal tubular lumen and interstitial infiltration of inflammatory cells were observed in RHR group, enalapril and irbesartan attenuated the above injuries. ConclusionsHypertensive renal damage may be associated with the increased of ACE and ACE2 ratio in kidney; The reversal effects of enalapril and irbesartan on hypertensive renal damage may be related to decreased ACE and ACE2 ratio.