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

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dc.catalogadorjlo
dc.contributor.authorMondaca Ruff, David Gonzalo
dc.contributor.authorAraos Valdebenito, Fernando Patricio
dc.contributor.authorYañez, Cristián
dc.contributor.authorNovoa, Ulises F.
dc.contributor.authorMora, Ítalo G.
dc.contributor.authorOcaranza Jeraldino, María Paz
dc.contributor.authorJalil Milad, Jorge Emilio
dc.date.accessioned2024-06-05T14:33:05Z
dc.date.available2024-06-05T14:33:05Z
dc.date.issued2021
dc.description.abstractBackground: Thiazides are one of the most common antihypertensive drugs used for hypertension treatment and hydrochlorothiazide (HCTZ) is the most frequently used diuretic for hypertension treatment. The Rho/Rho-kinase (ROCK) path plays a key function in cardiovascular remodeling. We hypothesized that in preclinical hypertension HCTZ reduces myocardial ROCK activation and consequent myocardial remodeling. Methods: The preclinical model of deoxycorticosterone (DOCA)-salt hypertension was used (Sprague–Dawley male rats). After 3 weeks, in 3 different groups: HCTZ, the ROCK inhibitor fasudil or spironolactone was added (3 weeks). After 6 weeks myocardial hypertrophy and fibrosis, cardiac levels of profibrotic proteins, mRNA levels (RT PCR) of pro remodeling and pro oxidative molecules and ROCK activity were determined. Results: Blood pressure, myocardial hypertrophy and fibrosis were reduced significantly by HCTZ, fasudil and spironolactone. In the heart, increased levels of the pro-fibrotic proteins Col-I, Col-III and TGF-β1 and gene expression of pro-remodeling molecules TGF-β1, CTGF, MCP-1 and PAI-1 and the pro-oxidative molecules gp91phox and p22phox were significantly reduced by HCTZ, fasudil and spironolactone. ROCK activity in the myocardium was increased by 54% (P < 0.05) as related to the sham group and HCTZ, spironolactone and fasudil, reduced ROCK activation to control levels. Conclusions: HCTZ reduced pathologic LVH by controlling blood pressure, hypertrophy and myocardial fibrosis and by decreasing myocardial ROCK activation, expression of pro remodeling, pro fibrotic and pro oxidative genes. In hypertension, the observed effects of HCTZ on the myocardium might explain preventive outcomes of thiazides in hypertension, specifically on LVH regression and incident heart failure.
dc.description.funderAgencia Nacional de Investigacion y Desarrollo
dc.description.funderFondecyt
dc.description.funderFONDAP
dc.format.extent12 páginas
dc.fuente.origenScopus
dc.identifier.doi10.1177/10742484211053109
dc.identifier.eissn19404034
dc.identifier.issn1074-2484
dc.identifier.pubmedid34623176
dc.identifier.scopusidSCOPUS_ID:85116788658
dc.identifier.urihttp://cpt.sagepub.com/archive/
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/86430
dc.information.autorucEscuela de Química; Mondaca Ruff, David Gonzalo; 0000-0001-9211-2963; 169847
dc.information.autorucEscuela de Medicina; Araos Valdebenito, Fernando Patricio; S/I; 70878
dc.information.autorucEscuela de Medicina; Ocaranza Jeraldino, María Paz; 0000-0002-4915-6378; 1001254
dc.information.autorucEscuela de Medicina; Jalil Milad, Jorge Emilio; 0000-0001-6877-2072; 99946
dc.issue.numero6
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final735
dc.pagina.inicio724
dc.revistaJournal of Cardiovascular Pharmacology and Therapeutics
dc.rightsacceso restringido
dc.subjectCardiac remodeling
dc.subjectHydrochlorothiazide
dc.subjectHypertension
dc.subjectHypertrophy
dc.subjectRho-kinase
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleHydrochlorothiazide Reduces Cardiac Hypertrophy, Fibrosis and Rho-Kinase Activation in DOCA-Salt Induced Hypertension
dc.typeartículo
dc.volumen26
sipa.codpersvinculados169847
sipa.codpersvinculados70878
sipa.codpersvinculados1001254
sipa.codpersvinculados99946
sipa.trazabilidadSCOPUS;21-03-2022
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