Upregulation of M3 muscarinic receptor inhibits cardiac hypertrophy induced by angiotensin II

被引：22

作者：

Liu, Yan ^{[1
]}

Wang, Shu ^{[1
,2
]}

Wang, Chao ^{[1
]}

Song, Haoxin ^{[1
]}

Han, Hongmei ^{[1
]}

Hang, Pengzhou ^{[1
,3
]}

Jiang, Yanan ^{[1
]}

Wei, Lanlan ^{[4
]}

Huo, Rong ^{[1
]}

Sun, Lihua ^{[1
]}

Gao, Xu ^{[5
]}

Lu, Yanjie ^{[1
]}

Du, Zhimin ^{[1
,3
]}

机构：

[1] Harbin Med Univ, Dept Pharmacol, State Prov Key Lab China, Harbin 150081, Heilongjiang, Peoples R China

[2] Harbin Med Univ, Affiliated Hosp 1, Dept Cardiac Care Unit, Harbin 150081, Heilongjiang, Peoples R China

[3] Harbin Med Univ, Hosp 2, Inst Clin Pharmacol, Harbin 150081, Heilongjiang, Peoples R China

[4] Dept Microbiol, Harbin 150081, Heilongjiang, Peoples R China

[5] Harbin Med Univ, Dept Biochem, Harbin, Heilongjiang, Peoples R China

来源：

JOURNAL OF TRANSLATIONAL MEDICINE | 2013年 / 11卷

基金：

中国国家自然科学基金;

关键词：

Cardiac hypertrophy; M-3 muscarinic acetylcholine receptor; Angiotensin II; Choline; ACETYLCHOLINE-RECEPTORS; DILATED CARDIOMYOPATHY; HEART-RATE; ACTIVATION; SUBTYPES; MICE;

D O I：

10.1186/1479-5876-11-209

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background: M-3 muscarinic acetylcholine receptor (M-3-mAChR) is stably expressed in the myocardium, but its pathophysiological role remains largely undefined. This study aimed to investigate the role of M-3-mAChR in cardiac hypertrophy induced by angiotensin II (Ang II) and elucidate the underlying mechanisms. Methods: Cardiac-specific M-3-mAChR overexpression transgenic (TG) mice and rat H9c2 cardiomyoblasts with ectopic expression of M-3-mAChR were established. Models of cardiac hypertrophy were induced by transverse aortic constriction (TAC) or Ang II infusion in the mice in vivo, and by isoproterenol (ISO) or Ang II treatment of H9c2 cells in vitro. Cardiac hypertrophy was evaluated by electrocardiography (ECG) measurement, hemodynamic measurement and histological analysis. mRNA and protein expression were detected by real-time RT-PCR and Western blot analysis. Results: M-3-mAChR was upregulated in hypertrophic heart, while M-2-mAChR expression did not change significantly. M-3-mAChR overexpression significantly attenuated the increased expression of atrial natriuretic peptide and beta-myosin heavy chain induced by Ang II both in vivo and in vitro. In addition, M-3-mAChR overexpression downregulated AT(1) receptor expression and inhibited the activation of MAPK signaling in the heart. Conclusion: The upregulation of M-3-mAChR during myocardial hypertrophy could relieve the hypertrophic response provoked by Ang II, and the mechanism may involve the inhibition of MAPK signaling through the downregulation of AT(1) receptor.

引用

页数：8

共 30 条

[1] Effects of p38 MAPK inhibitor on angiotensin II-dependent hypertension, organ damage, and superoxide anion production [J].