論文 - 詳細
| RRC ID | 81546 |
|---|---|
| 著者 | Ashenagar MS, Higashino T, Matsumoto A, Higashino H. |
| タイトル | Mechanisms of thiazide-induced hypertension treatment: insights from gene expression and histological analysis in malignant stroke-prone spontaneously hypertensive rats. |
| ジャーナル | J Hypertens |
| 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. |
| 公開日 | 2024-8-22 |
| DOI | 10.1097/HJH.0000000000003837 |
| PII | 00004872-990000000-00524 |
| PMID | 39206783 |
| PMC | PMC11556871 |
| MeSH | Animals Antihypertensive Agents / pharmacology Blood Pressure / drug effects Gene Expression / drug effects Hypertension / drug therapy Male Rats Rats, Inbred SHR* Stroke* / drug therapy Thiazides / pharmacology Thiobarbituric Acid Reactive Substances / metabolism |
| IF | 4.171 |
| リソース情報 | |
| ラット | This work was supported by the National Center for Biotechnology Information (NCBI), DNA Data Bank of Japan, and the National Bio Resource Project for Rats in Japan for access to their network servers. |