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[An experimental study of expression of angiotension converting enzyme 2 in myocardium and effect of telmisartan treatment in pressure-overloaded rats].
- Source :
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Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue [Zhongguo Wei Zhong Bing Ji Jiu Yi Xue] 2008 Apr; Vol. 20 (4), pp. 218-22. - Publication Year :
- 2008
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Abstract
- Objective: To study the effect of hypertension and telmisartan treatment on the protein and gene expression of cardiac angiotensin-converting enzyme 2 (ACE2) in pressure-overloaded rats.<br />Methods: Coarctation of suprarenal abdominal aorta was reproduced in 8 week-old male Sprague-Dawley (SD) rats and then randomized into 4 groups, including a sham group (n=15), a suprarenal aortic coarctation group (model group, n=12), a suprarenal aortic coarctation with low-dose Telmisartan treatment group (low-dose group, 2 mgxkg(-1)xd(-1), n=11) and a suprarenal aortic coarctation with high-dose Telmisartan treatment group(high-dose group, 10 mgxkg(-1)xd(-1), n=13). Telmisartan or equivalent amount of normal saline was gavaged 24 hours before the operation and once every day afterwards for 3 weeks. At the end of 3 weeks, the concentrations of angiotensin (AngII) in plasma and myocardium were measured by radioimmunoassay. Changes in both protein quantity and gene expressions of both ACE2 and ACE were determined by Western blotting analysis and reverse transcription-polymerase chain reaction (RT-PCR) technique, respectively.<br />Results: Suprarenal abdominal aortic coarctation induced a significant increase in the plasma and myocardium AngII concentration [plasma: (495.1+/-55.6) ng/L vs. (269.2+/-39.5)ng/L, myocardium: (103.6+/-23.7) ng/g vs. (49.5+/-13.5) ng/g, both P<0.01] and expressions of gene and protein of ACE (P<0.01) and ACE2 (P<0.05). Telmisartan further increased the concentration of AngII in plasma and myocardium in a dose-dependent manner [plasma: (702.2+/-40.6) ng/L vs. (612.6+/-35.5) ng/L, myocardium (211.5+/-21.5) ng/g vs. (189.6+/-43.6) ng/g, both P<0.05], and induced a dose-dependent increase in both protein and gene expression of ACE2 (protein 1.16+/-0.06 vs. 0.79+/-0.04, gene 0.54+/-0.08 vs. 0.41+/-0.04, both P<0.05). Expression of ACE2 protein in low-dose and high-dose groups was increased by 1.0 and 1.58 folds respectively, and gene was increased by 1.3 and 1.6 folds (all P<0.05). The expression of ACE protein and gene in model group increased significantly (protein: 2.10+/-1.07 vs. 1.02+/-0.05, gene: 1.93+/-0.09 vs. 0.26+/-0.09, both P<0.01). Telmisartan had no significant effect on ACE gene and protein expressions (both P>0.05).<br />Conclusion: Suprarenal abdominal aortic coarctation induced a significant increases of ACE and ACE2 gene and protein expressions. Telmisartan induces a dose-dependent increases of cardiac ACE2 gene and protein expression,which may be the mechanism of its therapeutic effects.
- Subjects :
- Angiotensin II metabolism
Angiotensin-Converting Enzyme 2
Animals
Aortic Coarctation drug therapy
Disease Models, Animal
Male
RNA, Messenger metabolism
Random Allocation
Rats
Rats, Sprague-Dawley
Telmisartan
Aortic Coarctation metabolism
Benzimidazoles pharmacology
Benzoates pharmacology
Myocardium metabolism
Peptidyl-Dipeptidase A metabolism
Subjects
Details
- Language :
- Chinese
- ISSN :
- 1003-0603
- Volume :
- 20
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue
- Publication Type :
- Academic Journal
- Accession number :
- 18419956