Zhao Jun, Liu Tiecheng, Liu Enzhao, Li Guangping, Qi Lingshan, Li Jian
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, People's Republic of China.
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, People's Republic of China
J Renin Angiotensin Aldosterone Syst. 2016 Mar 23;17(1):1470320315627409. doi: 10.1177/1470320315627409. Print 2016 Jan-Mar.
The objective of this article is to investigate the possible role of atrial natriuretic peptide (ANP) in Angiotensin-(1-7) (Ang-(1-7)) signaling pathway on atrial electrical and structural remodeling in a chronic rapid atrial pacing canine model.
Twenty-four dogs were randomly assigned to four groups: a sham group, paced control group, a paced + Ang-(1-7) group and a paced + Ang-(1-7) + A-71915 group. Atrial rapid pacing (ARP) at 600 bpm was maintained for 14 days except in the animals from the sham group. During the pacing, Ang-(1-7) (6 μg•kg-1•h-1) or Ang-(1-7) (6 μg•kg-1•h-1) + A-71915 (ANP receptor antagonist, 0.30 μg•kg-1•h-1) were given intravenously, respectively. After pacing, it was measured that electrophysiological parameters including atrial effective refractory periods (ERPs), inducibility and duration of atrial fibrillation (AF), ICaL and INa changed, where ICaL refers to voltage-dependent L-type Ca(2+) current and INa refers to cardiac sodium current. Then, the fibrosis and the expression of Cav1.2, INav1.5α subunit, TGF-β1 and ANP in atria were assessed.
After ARP, compared with the sham group, the atrial ERPs at six sites in each dog were shortened with the increasing in inducibility and duration of AF in the paced control group. The density of ICaL, INa and the expression of Cav1.2, INav1.5α subunit mRNA were decreased. Atrial tissue from the paced dogs showed significant interstitial fibrosis. The expression of TGF-β1 and ANP in mRNA and protein levels were increased. Compared with the paced control group, the shortening of atrial ERPs, and the increasing of inducibility and duration of AF induced by ARP were alleviated by Ang-(1-7) treatment (p < 0.05). The density of ICaL and INa and the expression of Cav1.2 and INav1.5α subunit mRNA were slightly decreased. Atrial tissue showed less interstitial fibrosis after Ang-(1-7) treatment. The increasing of ANP expression was improved by Ang-(1-7), while the increasing of TGF-β1 expression was alleviated by Ang-(1-7) (p < 0.05). A-71915 treatment blocked the beneficial effects of Ang-(1-7) on the aforementioned electrophysiological parameters and atrial fibrosis. And A-71915 treatment blocked Ang-(1-7), improving the expression of TGF-β1.
Ang-(1-7) prevented atrial structural and electrical remodeling induced by ARP. Furthermore, Ang-(1-7) promoted ANP secretion, and ANP played a crucial role in the cardiac protection of the former.
本文旨在研究在慢性快速心房起搏犬模型中，心房利钠肽（ANP）在血管紧张素 -（1 - 7）（Ang -（1 - 7））信号通路对心房电重构和结构重构中可能发挥的作用。
将24只犬随机分为四组：假手术组、起搏对照组、起搏 + Ang -（1 - 7）组和起搏 + Ang -（1 - 7）+ A - 71915组。除假手术组动物外，其余动物以600次/分钟的频率进行心房快速起搏（ARP），持续14天。起搏期间，分别静脉给予Ang -（1 - 7）（6 μg•kg-1•h-1）或Ang -（1 - 7）（6 μg•kg-1•h-1）+ A - 71915（ANP受体拮抗剂，0.30 μg•kg-1•h-1）。起搏后，测量包括心房有效不应期（ERP）、房颤（AF）的诱发性和持续时间、L型钙电流（ICaL）和钠电流（INa）等电生理参数的变化，其中ICaL指电压依赖性L型Ca(2+)电流，INa指心脏钠电流。然后，评估心房纤维化以及Cav1.2、INav1.5α亚基、转化生长因子 -β1（TGF -β1）和ANP的表达。
ARP后，与假手术组相比，起搏对照组中每只犬六个部位的心房ERP缩短，AF的诱发性和持续时间增加。ICaL、INa密度以及Cav1.2、INav1.5α亚基mRNA的表达降低。起搏犬的心房组织出现明显的间质纤维化。TGF -β1和ANP在mRNA和蛋白水平的表达增加。与起搏对照组相比，Ang -（1 - 7）治疗减轻了ARP诱导的心房ERP缩短以及AF诱发性和持续时间的增加（p < 0.05）。ICaL和INa密度以及Cav1.2和INav1.5α亚基mRNA的表达略有降低。Ang -（1 - 7）治疗后心房组织的间质纤维化减少。Ang -（1 - 7）改善了ANP表达的增加，同时减轻了TGF -β1表达的增加（p < 0.05）。A - 71915治疗阻断了Ang -（1 - 7）对上述电生理参数和心房纤维化的有益作用。并且A - 71915治疗阻断了Ang -（1 - 7），提高了TGF -β1的表达。
Ang -（1 - 7）可预防ARP诱导的心房结构和电重构。此外，Ang -（1 - 7）促进ANP分泌，且ANP在前者的心脏保护中起关键作用。
