PDF(Pubmed)
Abstract：
Salt-sensitive hypertension (SSHTN) is associated with M1 macrophage polarization and inflammatory responses, leading to inflammation-associated lymphangiogenesis and functional impairment across multiple organs, including kidneys and gonads. However, it remains unclear whether promoting M2 macrophage polarization can alleviate the hypertension, inflammation, and end organ damage in mice with salt sensitive hypertension (SSHTN). Male and female mice were made hypertensive by administering nitro-L-arginine methyl ester hydrochloride (L-NAME; 0.5 mg/ml) for 2 weeks in the drinking water, followed by a 2-week interval without any treatments, and a subsequent high salt diet for 3 weeks (SSHTN). AVE0991 (AVE) was intraperitoneally administered concurrently with the high salt diet. Control mice were provided standard diet and tap water. AVE treatment significantly attenuated BP and inflammation in mice with SSHTN. Notably, AVE promoted M2 macrophage polarization, decreased pro-inflammatory immune cell populations, and improved function in renal and gonadal tissues of mice with SSHTN. Additionally, AVE decreased lymphangiogenesis in the kidneys and testes of male SSHTN mice and the ovaries of female SSHTN mice. These findings highlight the effectiveness of AVE in mitigating SSHTN-induced elevated BP, inflammation, and end organ damage by promoting M2 macrophage polarization and suppressing pro-inflammatory immune responses. Targeting macrophage polarization emerges as a promising therapeutic approach for alleviating inflammation and organ damage in SSHTN. Further studies are warranted to elucidate the precise mechanisms underlying AVE-mediated effects and to assess its clinical potential in managing SSHTN.
摘要：
盐敏感性高血压（SSHTN）与M1巨噬细胞极化和炎症反应有关，导致炎症相关的淋巴管生成和多个器官的功能障碍，包括肾脏和性腺.然而,目前尚不清楚促进M2巨噬细胞极化是否能缓解高血压，炎症,盐敏感性高血压（SSHTN）小鼠的终末器官损害。通过在饮用水中给予硝基-L-精氨酸甲酯盐酸盐（L-NAME;0.5mg/mL）2周使雄性和雌性小鼠高血压，然后间隔2周不进行任何治疗，和随后的高盐饮食3周（SSHTN）。AVE0991(AVE)与高盐饮食同时腹膜内给药。向对照小鼠提供标准饮食和自来水。AVE处理显著减弱SSHTN小鼠的BP和炎症。值得注意的是,AVE促进M2巨噬细胞极化，减少促炎免疫细胞群，并改善SSHTN小鼠的肾脏和性腺组织功能。此外,AVE减少了雄性SSHTN小鼠的肾脏和睾丸以及雌性SSHTN小鼠的卵巢中的淋巴管生成。这些发现强调了AVE在缓解SSHTN引起的血压升高方面的有效性，炎症,并通过促进M2巨噬细胞极化和抑制促炎免疫反应来结束器官损伤。靶向巨噬细胞极化成为缓解SSHTN炎症和器官损伤的有希望的治疗方法。需要进一步的研究来阐明AVE介导作用的确切机制，并评估其在管理SSHTN方面的临床潜力。
