PDF(Pubmed)
Abstract：
The Renin-Angiotensin-Aldosterone System (RAAS) has been implicated in systemic and neurogenic hypertension. The infusion of RAAS inhibitors blunted arterial pressure and efficacy of use-dependent synaptic transmission in sympathetic ganglia. The current investigation aims to elucidate the impact of RAAS-mediated receptors on left ventricular cardiomyocytes and the role of the sarcolemma-bound carrier system in the heart of the hypertensive transgene model. A significant increase in mRNA and the protein expression for angiotensin II (AngII) receptor subtype-1 (AT1R) was observed in (mREN2)27 transgenic compared to the normotensive rodents. Concurrently, there was an upregulation in AT1R and a downregulation in the MAS1 proto-oncogene protein receptor as well as the AngII subtype-2 receptor in hypertensive rodents. There were modifications in the expressions of sarcolemma Na+-K+-ATPase, Na+-Ca2+ exchanger, and Sarcoendoplasmic Reticulum Calcium ATPase in the transgenic hypertensive model. These observations suggest chronic RAAS activation led to a shift in receptor balance favoring augmented cardiac contractility and disruption in calcium handling through modifications of membrane-bound carrier proteins and blood pressure. The study provides insight into mechanisms underlying RAAS-mediated cardiac dysfunction and highlights the potential value of targeting the protective arm of AngII in hypertension.
摘要：
肾素-血管紧张素-醛固酮系统（RAAS）与全身性和神经性高血压有关。RAAS抑制剂的输注降低了交感神经节的动脉压和使用依赖性突触传递的功效。当前的研究旨在阐明RAAS介导的受体对左心室心肌细胞的影响以及高血压转基因模型心脏中肌膜结合载体系统的作用。与正常血压的啮齿动物相比，在（mREN2）27转基因动物中观察到血管紧张素II（AngII）受体亚型1（AT1R）的mRNA和蛋白质表达显着增加。同时,在高血压啮齿类动物中,AT1R上调,MAS1原癌基因蛋白受体和AngII亚型2受体下调.肌膜Na+-K+-ATP酶的表达有修饰,Na+-Ca2+交换剂,和转基因高血压模型中的肌内质网钙ATP酶。这些观察结果表明，慢性RAAS激活导致受体平衡发生变化，有利于通过修饰膜结合的载体蛋白和血压来增强心脏收缩力和破坏钙处理。该研究提供了对RAAS介导的心脏功能障碍的潜在机制的见解，并强调了在高血压中靶向AngII保护臂的潜在价值。
