Hydrochlorothiazide Reduces Cardiac Hypertrophy, Fibrosis and Rho-Kinase Activation in DOCA-Salt Induced...

Area of Science:

• Cardiovascular Pharmacology
• Renal Physiology
• Molecular Cardiology

Background:

• Thiazides, particularly hydrochlorothiazide (HCTZ), are widely used antihypertensive medications.
• The Rho/Rho-kinase (ROCK) pathway is implicated in cardiovascular remodeling processes.
• This study investigated the effect of HCTZ on ROCK activation in preclinical hypertension.

Purpose of the Study:

• To determine if HCTZ reduces myocardial Rho/Rho-kinase (ROCK) activation in a preclinical model of hypertension.
• To assess the impact of HCTZ on myocardial hypertrophy, fibrosis, and gene expression related to remodeling and oxidative stress.
• To compare the effects of HCTZ with a ROCK inhibitor (fasudil) and spironolactone.

Main Methods:

• A deoxycorticosterone (DOCA)-salt hypertension model in male Sprague-Dawley rats was utilized.
• Rats were treated with HCTZ, fasudil, or spironolactone for 3 weeks.
• Evaluations included blood pressure, myocardial hypertrophy and fibrosis, cardiac protein and mRNA levels, and ROCK activity.

Main Results:

• HCTZ, fasudil, and spironolactone significantly reduced blood pressure, myocardial hypertrophy, and fibrosis.
• These treatments also decreased cardiac levels of pro-fibrotic proteins (Col-I, Col-III, TGF-β1) and expression of pro-remodeling and pro-oxidative genes.
• HCTZ effectively reduced elevated myocardial ROCK activity to control levels.

Conclusions:

• HCTZ mitigates pathological left ventricular hypertrophy (LVH) by controlling blood pressure and reducing myocardial ROCK activation.
• HCTZ decreases myocardial fibrosis and expression of pro-remodeling, pro-fibrotic, and pro-oxidative genes.
• The observed effects of HCTZ on the myocardium may explain the preventive role of thiazides in hypertension, particularly in LVH regression and heart failure prevention.