Mechanisms of thiazide-induced hypertension treatment: insights from gene expression and histological analysis in malignant stroke-prone spontaneously hypertensive rats.

IF 3.3 2区 医学 Q1 PERIPHERAL VASCULAR DISEASE Journal of Hypertension Pub Date : 2024-12-01 Epub Date: 2024-08-21 DOI:10.1097/HJH.0000000000003837
Mohammad Said Ashenagar, Toshihide Higashino, Akiko Matsumoto, Hideaki Higashino
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Abstract

Objective: Diuretics, including thiazides and thiazide-like drugs, are commonly recommended for treating hypertension, though their precise mechanism of action is not fully understood. This study aimed to investigate the pharmacological effects of trichloromethiazide (TCM) in malignant stroke-prone spontaneously hypertensive rats (M-SHRSP).

Methods: M-SHRSPs were treated with varying doses of TCM. Prognosis, histological changes, and mRNA expression related to hypertension and stroke were assessed.

Results: The high-dose TCM group (3%) exhibited significantly lower SBP compared with the untreated group, whereas the low-dose group (0.3%) did not show a significant reduction in SBP. The survival rate was 54% in the low-dose group, whereas all rats in the high-dose group survived without experiencing a stroke by 16 weeks of age. Organ weights in both TCM-treated groups were lower than those in the control group, without severe histological abnormalities, including stroke and sclerosis. Plasma levels of thiobarbituric acid-reactive substances (TBARS) were significantly reduced in both TCM-treated groups. Additionally, 20 genes related to tissue protection, repair, proliferation, maintenance, and function were significantly expressed.

Conclusion: TCM administration in M-SHRSPs significantly modulated the expression of 20 genes associated with tissue protection and maintenance, and reduced plasma TBARS levels. These findings suggest that TCM, a thiazide diuretic, may protect against tissue impairment in hypertension by modulating gene expression and exhibiting antioxidant activity.

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噻嗪类药物诱导的高血压治疗机制:从恶性中风自发性高血压大鼠的基因表达和组织学分析中获得的启示。
目的:利尿剂,包括噻嗪类和类似噻嗪类药物,是治疗高血压的常用药物,但其确切的作用机制尚不完全清楚。本研究旨在探讨三氯噻嗪(TCM)对恶性中风易发自发性高血压大鼠(M-SHRSP)的药理作用:方法:用不同剂量的中药治疗M-SHRSP。方法:用不同剂量的中药治疗 M-SHRSP 大鼠,评估其预后、组织学变化以及与高血压和中风相关的 mRNA 表达:结果:与未治疗组相比,高剂量中药组(3%)的 SBP 明显降低,而低剂量组(0.3%)的 SBP 没有明显降低。低剂量组大鼠的存活率为 54%,而高剂量组大鼠在 16 周龄前全部存活,没有发生中风。中药治疗组和对照组的器官重量均低于对照组,但未出现严重的组织学异常,包括中风和硬化。中药治疗组和对照组血浆中硫代巴比妥酸反应物质(TBARS)水平均显著降低。此外,20个与组织保护、修复、增殖、维护和功能相关的基因也有明显表达:结论:对 M-SHRSPs 施用中药可明显调节 20 个与组织保护和维护相关的基因的表达,并降低血浆 TBARS 水平。这些研究结果表明,中药作为一种噻嗪类利尿剂,可通过调节基因表达和抗氧化活性来保护高血压患者的组织免受损伤。
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来源期刊
Journal of Hypertension
Journal of Hypertension 医学-外周血管病
CiteScore
7.90
自引率
6.10%
发文量
1389
审稿时长
3 months
期刊介绍: The Journal of Hypertension publishes papers reporting original clinical and experimental research which are of a high standard and which contribute to the advancement of knowledge in the field of hypertension. The Journal publishes full papers, reviews or editorials (normally by invitation), and correspondence.
期刊最新文献
Response to commentary by Andrew Sharp et al. Targeting the sympathetic nervous system with the selective imidazoline receptor agonist moxonidine for the management of hypertension: an international position statement. Abnormal brain-heart electrophysiology in mild and severe orthostatic hypotension. Mechanisms of thiazide-induced hypertension treatment: insights from gene expression and histological analysis in malignant stroke-prone spontaneously hypertensive rats. Aortic reservoir-excess pressure parameters are associated with worse cognitive function in people with untreated stage II/III hypertension.
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