Gkousioudi Anastasia, Razzoli Margherita, Moreira Jesse D, Wainford Richard D, Zhang Yanhang
Boston University.
Boston University Avedisian and Chobanian School of Medicine.
Res Sq. 2023 Sep 5:rs.3.rs-3273236. doi: 10.21203/rs.3.rs-3273236/v1.
The prevalence of hypertension increases with aging and is associated with increased arterial stiffness. Resistant hypertension is presented when drug treatments fail to regulate a sustained increased blood pressure. Given that the mechanisms between the sympathetic nervous system and the kidney play an important role in blood regulation, renal denervation (RDN) has emerged as a therapeutic potential in resistant hypertension. In this study, we investigated the effects of RDN on the biomechanical response and microstructure of elastic arteries. Common carotid arteries (CCA) were excised from 3-, 8- and 8-month-old denervated rats, and subjected to biaxial extension-inflation test. Our results showed that hypertension developed in the 8-month-old rats. The sustained elevated blood pressure resulted in arterial remodeling which was manifested as a significant stress increase in both axial and circumferential directions after 8 months. RDN had a favorable impact on CCAs with a restoration of stresses in values similar to control arteries at 3 months. After biomechanical testing, arteries were imaged under a multi-photon microscope to identify microstructural changes in extracellular matrix (ECM). Quantification of multi-photon images showed no significant alterations of the main ECM components, elastic and collagen fibers, indicating that arteries remained intact after RDN. Regardless of the experimental group, our microstructural analysis of the multi-photon images revealed that reorientation of the collagen fibers might be the main microstructural mechanism taking place during pressurization with their straightening happening during axial stretching.
高血压的患病率随年龄增长而增加，且与动脉僵硬度增加有关。当药物治疗未能调节持续升高的血压时，即出现顽固性高血压。鉴于交感神经系统和肾脏之间的机制在血压调节中起重要作用，肾去神经支配（RDN）已成为治疗顽固性高血压的一种潜在方法。在本研究中，我们研究了RDN对弹性动脉生物力学反应和微观结构的影响。从3个月、8个月和8个月大的去神经大鼠中切除颈总动脉（CCA），并进行双轴拉伸-充气试验。我们的结果表明，8个月大的大鼠出现了高血压。持续升高的血压导致动脉重塑，表现为8个月后轴向和周向应力均显著增加。RDN对CCA有良好影响，应力恢复到与3个月大的对照动脉相似的值。在生物力学测试后，在多光子显微镜下对动脉进行成像，以识别细胞外基质（ECM）的微观结构变化。多光子图像定量显示，主要ECM成分、弹性纤维和胶原纤维无显著改变，表明RDN后动脉保持完整。无论实验组如何，我们对多光子图像的微观结构分析表明，胶原纤维的重新定向可能是加压过程中发生的主要微观结构机制，其在轴向拉伸过程中伸直。
