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

Author:

Ashenagar Mohammad Said12,Higashino Toshihide3,Matsumoto Akiko1,Higashino Hideaki2

Affiliation:

1. Department of Social and Environmental Medicine, Faculty of Medicine, Saga University, Saga

2. Department of Pharmacology, Kindai University School of Medicine, Osaka-Sayama-city, Osaka

3. Department of Dermatology, Self-Defense Forces Central Hospital, Setagaya-ward, Tokyo, Japan

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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