Department of Foundational Sciences, East Carolina School of Dental Medicine, Greenville, NC 27834, USA.
Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Int J Mol Sci. 2024 Jun 26;25(13):6997. doi: 10.3390/ijms25136997.
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 (ATR) was observed in (mREN2)27 transgenic compared to the normotensive rodents. Concurrently, there was an upregulation in ATR 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-Ca 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.
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 抑制剂的输注可减弱动脉压，并降低交感神经节中使用依赖性突触传递的效率。目前的研究旨在阐明 RAAS 介导的受体对左心室心肌细胞的影响，以及在高血压转基因模型的心脏中，肌浆网结合载体系统的作用。与正常血压啮齿动物相比，（mREN2）27 转基因动物的血管紧张素 II（AngII）受体亚型-1（ATR）的 mRNA 和蛋白表达显著增加。同时，ATR 的表达上调，MAS1 原癌基因蛋白受体以及 AngII 亚型-2 受体的表达下调。在转基因高血压模型中，肌浆网 Na-K-ATP 酶、Na-Ca 交换器和肌浆网内质网钙 ATP 酶的表达发生改变。这些观察结果表明，慢性 RAAS 激活导致受体平衡发生变化，有利于心脏收缩力增强，并通过改变膜结合载体蛋白和血压来破坏钙处理。该研究深入了解了 RAAS 介导的心脏功能障碍的机制，并强调了靶向 AngII 的保护作用在高血压中的潜在价值。
