title: [Telmisartan reduces retina vessel endothelial cell apoptosis via upregulating retinal ACE2-Ang-(1-7)-Mas axis in spontaneous hypertensive rats].
abstract: OBJECTIVE
  To investigate the effects of angiotensin II (Ang II) antagonist telmisartan on retina vessel endothelial cell apoptosis and its impact on the ACE2-Ang-(1-7)-Mas axis in spontaneous hypertensive rats (SHR).
  
  
  METHODS
  Thirty-six SHR 16 week-old were randomly divided into 3 groups (n = 12 each): SHR, SHRT (telmisartan 10 mg · kg-1 · d-1 by gastric gavage) and SHRTA group (telmisartan 10 mg · kg-1 · d-1 by gastric gavage plus intravenous injection of A-779 0.5 mg · kg-1 · d-1), twelve WKY rats served as normotensive control group. Systolic blood pressure was measured at pre-treatment and 8 weeks later. After 8 weeks, rats were sacrificed, the expression of ACE2 and Mas in retina were analyzed by qRT-PCR, Western blot and Immunohistochemistry, the Ang-(1-7) concentration in serum was measured by ELISA. Specimens were obtained and stained by hematoxylin and eosin, and the morphology of retina vessel was observed. Apoptosis of vessel endothelial cells were determined by using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling method.
  
  
  RESULTS
  The systolic blood pressure of SHR, SHRT and SHRTA groups at baseline were significantly higher than age-matched WKY group (all P < 0.01). Eight weeks later, the systolic blood pressure group was significantly lower in SHRT group than in the SHR group (P < 0.01), this effect was partly reversed in SHRTA group. The retinal ACE2 mRNA and protein expression was significantly lower in SHR group than in WKY and SHRT groups (P < 0.01), which was similar between SHRT group and SHRTA group (P > 0.05). The retinal Mas mRNA and protein expression were significantly lower in SHR group compared to WKY and SHRT groups (all P < 0.01), which was significantly lower in SHRTA group than in the SHRT group (P < 0.05). ELISA results showed that serum Ang-(1-7) protein level was significantly lower in SHR group than in WKY group and SHRT group (both P < 0.05), which was lower in SHRTA group compared to SHRT group. Retinal vessel endothelial cell apoptosis was higher in SHR group than in WKY group, which could be reduced by cotreatment with telmisartan and this beneficial effect could be reversed by A-779.
  
  
  CONCLUSIONS
  Telmisartan can reduce retinal vessel endothelial cell apoptosis via upregulating the ACE2-Ang-(1-7)-Mas axis.
authors.affiliation: Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Zhenhao
authors.initials: Z
authors.lastname: Lin
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Ni
authors.forename: Lianglei
authors.initials: L
authors.lastname: Hou
authors.forename: Lijuan
authors.initials: L
authors.lastname: Song
authors.forename: Yihao
authors.initials: Y
authors.lastname: Wu
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Hu
authors.forename: Juhong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Email: deyeyang@126.com.
authors.forename: Deye
authors.initials: D
authors.lastname: Yang
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure; D042783:Endothelial Cells; D010446:Peptide Fragments / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012160:Retina; D013599:Systole; D000077333:Telmisartan; D015854:Up-Regulation
chemical_list: C092006:7-Ala-angiotensin (1-7); D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7); D000077333:Telmisartan