关键词: Antihypertensive medications Excessive sodium intake High-salt diet Hypertension Immunomodulation Macrophages

Mesh : Animals Antihypertensive Agents / pharmacology Macrophages / drug effects metabolism immunology Mice Inflammation / drug therapy Macrophage Activation / drug effects Hypertension / chemically induced drug therapy immunology Male Cytokines / metabolism Phagocytosis / drug effects Sodium, Dietary / adverse effects Inflammation Mediators / metabolism

来  源:   DOI:10.1016/j.biopha.2024.116648

Abstract:
Nowadays, there is an increasing emphasis on the need to alleviate the chronic inflammatory response to effectively treat hypertension. However, there are still gaps in our understanding on how to achieve this. Therefore, research on interaction of antihypertensive drugs with the immune system is extremely interesting, since their therapeutic effect could partly result from amelioration of hypertension-related inflammation, in which macrophages seem to play a pivotal role. Thus, current comprehensive studies have investigated the impact of repeatedly administered hypotensive drugs (captopril, olmesartan, propranolol, carvedilol, amlodipine, verapamil) on macrophage functions in the innate and adaptive immunity, as well as if drug-induced effects are affected by a high-sodium diet (HSD), one of the key environmental risk factors of hypertension. Although the assayed medications increased the generation of reactive oxygen and nitrogen intermediates by macrophages from standard fed donors, they reversed HSD-induced enhancing effects on macrophage oxidative burst and secretion of pro-inflammatory cytokines. On the other hand, some drugs increased macrophage phagocytic activity and the expression of surface markers involved in antigen presentation, which translated into enhanced macrophage ability to activate B cells for antibody production. Moreover, the assayed medications augmented macrophage function and the effector phase of contact hypersensitivity reaction, but suppressed the sensitization phase of cell-mediated hypersensitivity under HSD conditions. Our current findings contribute to the recognition of mechanisms, by which excessive sodium intake affects macrophage immune activity in hypertensive individuals, and provide evidence that the assayed medications mitigate most of the HSD-induced adverse effects, suggesting their additional protective therapeutic activity.
摘要:
如今,人们越来越重视缓解慢性炎症反应以有效治疗高血压。然而,我们对如何实现这一目标的理解仍然存在差距。因此,抗高血压药物与免疫系统相互作用的研究非常有趣,因为它们的治疗效果可能部分来自高血压相关炎症的改善,其中巨噬细胞似乎起着关键作用。因此,目前的综合研究已经调查了反复服用降压药的影响(卡托普利,奥美沙坦,普萘洛尔,卡维地洛,氨氯地平,维拉帕米)对先天和适应性免疫中的巨噬细胞功能,以及如果药物诱导的作用受到高钠饮食(HSD)的影响,高血压的关键环境危险因素之一。尽管被测定的药物增加了来自标准饲喂供体的巨噬细胞的活性氧和氮中间体的产生,他们逆转了HSD诱导的巨噬细胞氧化爆发和促炎细胞因子分泌的增强作用.另一方面,一些药物增加巨噬细胞吞噬活性和参与抗原呈递的表面标志物的表达,转化为增强的巨噬细胞激活B细胞以产生抗体的能力。此外,所测定的药物增强了巨噬细胞功能和接触超敏反应的效应相,但抑制了HSD条件下细胞介导的超敏反应的致敏阶段。我们目前的发现有助于对机制的认识,过量的钠摄入会影响高血压个体的巨噬细胞免疫活性,并提供证据证明所测定的药物可以减轻大部分HSD引起的不良反应,表明它们具有额外的保护性治疗活性。
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