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血管紧张素转换酶和血管紧张素转换酶 2 参与了大鼠主动脉神经切断诱导的心血管肥大。

Angiotensin-converting enzyme and Angiotensin-converting enzyme 2 are involved in sinoaortic denervation-induced cardiovascular hypertrophy in rats.

机构信息

Department of Pharmacy, Shanghai Seventh People's Hospital, Shanghai 200137, China.

出版信息

Biol Pharm Bull. 2011;34(9):1398-403. doi: 10.1248/bpb.34.1398.

Abstract

The balance of angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) in high blood pressure variability (BPV) induced cardiovascular hypertrophy remains elusive. The aim of the present work was to investigate expression and activity of ACE and ACE2 in the heart and aorta of sinoaortic denervation (SAD) rats with high BPV and normal BP, and explore the potential role of ACE and ACE2 in high BPV-induced cardiovascular damage. Hemodynamics, cardiovascular hypertrophy, angiotensin II (Ang II) concentrations, ACE and ACE2 activity were determined. Cardiac-tissue ACE and ACE2 expression were assayed by real-time polymerase chain reaction and Western blot. Compared with sham-operated rats, systolic BPV and diastolic BPV increased and baroreflex sensitivity decreased significantly in SAD rats. SAD rats presented with obvious cardiovascular hypertrophy characterized by increased ratio of left ventricle weight to body weight and aortic weight to the length of aorta. There was no difference in plasma Ang II concentration between sham-operated and SAD rats. The cardiac and aortic ACE expression, aortic ACE2 expression and ACE activity were elevated in SAD rats. There was no significant difference in cardiac ACE2 expressions between sham-operated and SAD rats. The present work demonstrated that cardiac and aortic ACE expression, aortic ACE2 expression and ACE activity were increased in SAD rats. It is the tissue rather than the circulating renin-angiotensin system that contributes to high BPV-induced cardiovascular hypertrophy.

摘要

在高血压变异性(BPV)引起的心血管肥大中,血管紧张素转换酶(ACE)和血管紧张素转换酶 2(ACE2)的平衡仍不清楚。本研究旨在探讨高 BPV 和正常 BP 的去窦神经大鼠心脏和主动脉中 ACE 和 ACE2 的表达和活性,并探讨 ACE 和 ACE2 在高 BPV 诱导的心血管损伤中的潜在作用。测定血流动力学、心血管肥大、血管紧张素 II(Ang II)浓度、ACE 和 ACE2 活性。通过实时聚合酶链反应和 Western blot 测定心脏组织 ACE 和 ACE2 的表达。与假手术大鼠相比,去窦神经大鼠的收缩压变异性和舒张压变异性明显增加,压力反射敏感性明显降低。去窦神经大鼠表现出明显的心血管肥大,表现为左心室重量与体重比和主动脉重量与主动脉长度比增加。血浆 Ang II 浓度在假手术和去窦神经大鼠之间无差异。去窦神经大鼠的心脏和主动脉 ACE 表达、主动脉 ACE2 表达和 ACE 活性升高。假手术和去窦神经大鼠的心脏 ACE2 表达无显著差异。本研究表明,去窦神经大鼠的心脏和主动脉 ACE 表达、主动脉 ACE2 表达和 ACE 活性增加。是组织而不是循环肾素-血管紧张素系统导致了高 BPV 诱导的心血管肥大。

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