In Vivo and In Vitro Effects of Vasopressin V2 Receptor Antagonism on Myocardial Fibrosis in Rats.
Am J Med Sci
; 357(2): 151-159, 2019 02.
Article
en En
| MEDLINE
| ID: mdl-30665496
ABSTRACT
BACKGROUND:
Myocardial fibrosis is a major pathophysiologic substrate of heart failure with preserved ejection fraction. Vasopressin is an important therapeutic target in heart failure with preserved ejection fraction since it can modulate fluid balance, and based on a few studies, myocardial matrix deposition. Hence we examined the role of vasopressin antagonism in modulating myocardial matrix metabolism in vivo and in vitro. MATERIALS ANDMETHODS:
In vivo studies utilized an established model of hyperhomocysteinemia-induced myocardial fibrosis in Sprague-Dawley rats combined with high salt diet; in vivo studies also utilized the same profibrotic stimuli of homocysteine and NaCl in cultured rat cardiac fibroblasts.RESULTS:
Hyperhomocysteinemia combined with high-salt diet promoted myocardial fibrosis, profibrotic and matrix gene expression and tolvaptan attenuated all these in vivo effects. In cultured cardiac fibroblasts, combined treatment with homocysteine and NaCl increased profibrotic and matrix gene expression and activation of PI3/Akt pathway; all these effects were attenuated by tolvaptan Vasopressin levels, gene expression and V2 receptor expression were increased in vivo and in vitro on exposure to profibrotic stimuli, and tolvaptan attenuated these in vivo and in vitro effects.CONCLUSIONS:
Antagonism of vasopressin V2 receptor, via direct actions on cardiac fibroblast, attenuates myocardial matrix deposition.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibrosis
/
Antagonistas de los Receptores de Hormonas Antidiuréticas
/
Tolvaptán
/
Insuficiencia Cardíaca
/
Cardiomiopatías
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Med Sci
Año:
2019
Tipo del documento:
Article