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

David Mondaca-Ruff1, Patricio Araos1,2, Cristián E Yañez1

  • 1Laboratory of Molecular Cardiology, Division of Cardiovascular Diseases, School of Medicine, 60709Pontificia Universidad Católica de Chile, Santiago, Chile.

Journal of Cardiovascular Pharmacology and Therapeutics
|October 8, 2021
PubMed

Insights

Hydrochlorothiazide (HCTZ) reduces hypertension-related myocardial remodeling by lowering blood pressure and inhibiting Rho-kinase (ROCK) activation. This study shows HCTZ effectively decreases cardiac hypertrophy and fibrosis in preclinical hypertension models.

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.
Abstract

Keywords:
Rho-kinasecardiac remodelinghydrochlorothiazidehypertensionhypertrophy

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