Simko Fedor, Baka Tomas, Stanko Peter, Repova Kristina, Krajcirovicova Kristina, Aziriova Silvia, Domenig Oliver, Zorad Stefan, Adamcova Michaela, Paulis Ludovit
Institute of Pathophysiology, Faculty of Medicine, Comenius University, 81108 Bratislava, Slovakia.
3rd Department of Internal Medicine, Faculty of Medicine, Comenius University, 83305 Bratislava, Slovakia.
Biomedicines. 2022 Jul 31;10(8):1844. doi: 10.3390/biomedicines10081844.
This study investigated whether sacubitril/valsartan and ivabradine are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in a rat experimental model of spontaneous hypertension (spontaneously hypertensive rats, SHRs) and whether this potential protection is associated with RAAS alterations. Five groups of three-month-old male Wistar rats and SHRs were treated for six weeks as follows: untreated Wistar controls, Wistar plus sacubitril/valsartan, SHR, SHR plus sacubitril/valsartan, and SHR plus ivabradine. The SHRs developed a systolic blood pressure (SBP) increase, LV hypertrophy and fibrosis, and LV systolic and diastolic dysfunction. However, no changes in serum RAAS were observed in SHRs compared with the controls. Elevated SBP in SHRs was decreased by sacubitril/valsartan but not by ivabradine, and only sacubitril/valsartan attenuated LV hypertrophy. Both sacubitril/valsartan and ivabradine reduced LV collagen content and attenuated LV systolic and diastolic dysfunction. Sacubitril/valsartan increased the serum levels of angiotensin (Ang) II, Ang III, Ang IV, Ang 1-5, Ang 1-7, and aldosterone, while ivabradine did not affect the RAAS. We conclude that the SHR is a normal-to-low serum RAAS model of experimental hypertension. While the protection of the hypertensive heart in SHRs by sacubitril/valsartan may be related to an Ang II blockade and the protective Ang 1-7, the benefits of ivabradine were not associated with RAAS modulation.
本研究调查了沙库巴曲缬沙坦和伊伐布雷定是否能够预防自发性高血压大鼠（SHRs）实验模型中的左心室（LV）纤维化重塑和功能障碍，以及这种潜在的保护作用是否与肾素-血管紧张素-醛固酮系统（RAAS）改变有关。将五组三个月大的雄性Wistar大鼠和SHRs按以下方式治疗六周：未治疗的Wistar对照组、Wistar加沙库巴曲缬沙坦、SHR、SHR加沙库巴曲缬沙坦以及SHR加伊伐布雷定。SHRs出现收缩压（SBP）升高、左心室肥厚和纤维化以及左心室收缩和舒张功能障碍。然而，与对照组相比，SHRs的血清RAAS未观察到变化。沙库巴曲缬沙坦可降低SHRs升高的SBP，但伊伐布雷定不能，且只有沙库巴曲缬沙坦可减轻左心室肥厚。沙库巴曲缬沙坦和伊伐布雷定都可降低左心室胶原含量并减轻左心室收缩和舒张功能障碍。沙库巴曲缬沙坦可提高血清血管紧张素（Ang）II、Ang III、Ang IV、Ang 1-5、Ang 1-7和醛固酮水平，而伊伐布雷定不影响RAAS。我们得出结论，SHR是实验性高血压的血清RAAS正常至低水平模型。虽然沙库巴曲缬沙坦对SHRs高血压心脏的保护作用可能与Ang II阻断和具有保护作用的Ang 1-7有关，但伊伐布雷定的益处与RAAS调节无关。
