Effect Of Angiotensin-coverting Enzyme 2 On The Regression Of Vascular Remodeling Of Losartan In The Renovascular Hypertensive Rats

Aim: Angiotensin-coverting enzyme 2 (ACE2), a newly recognized homology of ACE that converts angiotenin II (Ang II) to angiotensin 1-7 (Ang 1-7), is found in the vascular smooth muscle cell, and involves in the vascular function as well. In the present study, we investigated the regression of vascular remodeling of losartan and the expression of expression of ACE2 in the two-kidney-one-clip hypertensive rats.Methods: Two-kidney, one-clip (2K1C) hypertensive rat model was used in the experiment, blood pressure (BP) was measured by tail-cuff method. At the end of the experiment, the whole body of one part of rats was perfusion with phosphate buffer saline and followed by fixed in situ with the 4% paraformaldehyde, aortic and mesenteric artery sections were sheared and preserved in 10% formalin for morphological analysis. The remodeling parameter was calculated by the software in the computer. The level of protein of ACE or ACE2 was determined by western blotting. The expression of ACE or ACE2 mRNA was detected by RT-PCR in mesentery arteries or thoracic aorta.Results: Chronic administration of losartan caused a dose-dependent depressor effect on the blood pressure and hypertrophic artery in 2K1C hypertensive rats. The ratio of Media cross-sectional area (MCSA) to lumen area (LA) and the medium thickness (MT) to lumen diameter (LD) of mesenteric arteries in the losartan treated hypertensive rats are significantly decreased compared with non-treated hypertensive rats. Meanwhile, the ratio of ACE to ACE2 in the mRNA and protein was significantly increased in the non-treated hypertensive rats compared with the sham operation rats (1.53±0.03,0.81±0.02, P < 0.01 ).Treatment of losartan can decrease the ratio of ACE to ACE2, and there are relationship between the vascular remodeling parameters (MCSA/ LA, MT / LD) and the expression of ACE2 (P<0.05, P<0.01).Conclusion: The effects of Losartan on the hypotension and regression of vascular remodeling are related to increase of the expression of ACE2 and decrease of the expression of ACE.