血管紧张素II 1型受体阻滞剂的使用可预防HIV患者的氧化应激和肌肉功能障碍。

Angiotensin II Type 1 Receptor Blocker Usage Prevents Oxidative Stress and Muscle Dysfunction in HIV.

作者信息

Deminice Rafael, Cella Paola Sanches, Borsari Ana Lúcia, Padilha Camila S, de Oliveira Vitor Hugo Fernando

机构信息

Physical Education and Sports Institute, State University of Londrina, Londrina, Brazil.

Biology of Ageing Laboratory, Centre for Healthy Ageing, Centenary Institute of Cancer Medicine and Cell Biology, Royal Prince Alfred Hospital, Sidney, NSW, Australia.

出版信息

Fundam Clin Pharmacol. 2025 Aug;39(4):e70016. doi: 10.1111/fcp.70016.

DOI:10.1111/fcp.70016

PMID:40421794

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12108033/

Abstract

BACKGROUND

We aimed to elucidate the role of Angiotensin II type 1 receptor (AT1R) blocker usage in muscle wasting and dysfunction related to HIV.

RESEARCH DESIGN AND METHODS

Appendicular skeletal muscle mass, higher and lower limb strength, and physical fitness were determined in people living with HIV (PWH) using AT1R blockers users (n = 33), angiotensin-converting enzyme (ACE) inhibitors (n = 28), or not using antihypertensive drugs (n = 33). Groups had similar age, sex, race, BMI, and time of HIV infection. Muscle biopsies were performed to determine the abundance of AT1R, the relative abundance of selected proteins related to proteolysis, antioxidant enzymes, and oxidative stress. Plasma angiotensin II, IL-6, and TNF-alpha were also determined.

RESULTS

PWH using AT1R blocker presented higher strength, physical fitness, and muscle mass than PWH using ACE inhibitors or not using antihypertensive drugs. Although both PWH using AT1R blockers and ACE inhibitors presented reduced angiotensin II plasma levels, only PWH using AT1R blockers presented lower skeletal muscle AT1R activation, lower plasma oxidative stress markers, lower skeletal muscle oxidative stress (4-HNE), and proteolysis markers (Atrogin-1, Murf-1).

CONCLUSION

AT1R blocker usage protects against oxidative stress and activated proteolysis, contributing to the prevention of muscle wasting and dysfunction among PWH.

摘要

背景

我们旨在阐明1型血管紧张素II受体（AT1R）阻滞剂的使用在与HIV相关的肌肉萎缩和功能障碍中的作用。

研究设计与方法

使用AT1R阻滞剂的HIV感染者（PWH）（n = 33）、血管紧张素转换酶（ACE）抑制剂使用者（n = 28）或未使用抗高血压药物的PWH（n = 33），测定其四肢骨骼肌质量、上下肢力量和体能。各组在年龄、性别、种族、BMI和HIV感染时间方面相似。进行肌肉活检以确定AT1R的丰度、与蛋白水解、抗氧化酶和氧化应激相关的选定蛋白质的相对丰度。还测定了血浆血管紧张素II、IL-6和TNF-α。

结果

使用AT1R阻滞剂的PWH比使用ACE抑制剂或未使用抗高血压药物的PWH具有更高的力量、体能和肌肉质量。尽管使用AT1R阻滞剂和ACE抑制剂的PWH血浆血管紧张素II水平均降低，但只有使用AT1R阻滞剂的PWH骨骼肌AT1R激活程度较低、血浆氧化应激标志物较低、骨骼肌氧化应激（4-HNE）和蛋白水解标志物（Atrogin-1、Murf-1）较低。