School of Pharmacy, Minzu University of China, Beijing 100081, China.
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
Molecules. 2023 Feb 15;28(4):1844. doi: 10.3390/molecules28041844.
Hypertension in adolescents is associated with adverse cardiac and vascular events. In addition to lowering blood pressure, it is not clear whether pharmacological therapy in early life can improve vascular remodeling. This study aimed to evaluate the effects of long-term administration of losartan, aspirin, and atorvastatin on vascular remodeling in juvenile spontaneously hypertensive rats (SHRs). Losartan, aspirin, and atorvastatin were administered via gavage at doses of 20, 10, and 10 mg/kg/day, respectively, on SHRs aged 6-22 weeks. Paraffin sections of the blood vessels were stained with hematoxylin-eosin (H&E) and Sirius Red to evaluate the changes in the vascular structure and the accumulation of different types of collagen. The plasma levels of renin, angiotensin II (Ang II), aldosterone (ALD), endothelin-1 (ET-1), interleukin-6 (IL-6), and neutrophil elastase (NE) were determined using ELISA kits. After the 16-week treatment with losartan, aspirin, and atorvastatin, the wall thickness of the thoracic aorta and carotid artery decreased. The integrity of the elastic fibers in the tunica media was maintained in an orderly manner, and collagen deposition in the adventitia was retarded. The plasma levels of renin, ALD, ET-1, IL-6, and NE in the SHRs also decreased. These findings suggest that losartan, aspirin, and atorvastatin could improve vascular remodeling beyond their antihypertensive, anti-inflammatory, and lipid-lowering effects. Many aspects of the protection provided by pharmacological therapy are important for the prevention of cardiovascular diseases in adults and older adults.
青少年高血压与不良心脏和血管事件有关。除了降低血压外,早期生活中的药物治疗是否能改善血管重塑尚不清楚。本研究旨在评估长期给予氯沙坦、阿司匹林和阿托伐他汀对幼年自发性高血压大鼠(SHR)血管重塑的影响。氯沙坦、阿司匹林和阿托伐他汀分别以 20、10 和 10mg/kg/天的剂量通过灌胃给予 6-22 周龄的 SHR。用苏木精-伊红(H&E)和天狼星红染色血管石蜡切片,评估血管结构变化和不同类型胶原的积累。用 ELISA 试剂盒测定血浆肾素、血管紧张素 II(Ang II)、醛固酮(ALD)、内皮素-1(ET-1)、白细胞介素-6(IL-6)和中性粒细胞弹性蛋白酶(NE)水平。经过 16 周氯沙坦、阿司匹林和阿托伐他汀治疗后,胸主动脉和颈动脉壁厚度降低。中膜弹性纤维的完整性保持有序,外膜胶原沉积得到延缓。SHR 血浆肾素、ALD、ET-1、IL-6 和 NE 水平也降低。这些发现表明,氯沙坦、阿司匹林和阿托伐他汀除了具有降压、抗炎和降血脂作用外,还能改善血管重塑。药物治疗提供的许多保护方面对预防成人和老年人的心血管疾病非常重要。