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Eur J Pharmacol ; 933: 175254, 2022 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-36087696

RESUMEN

Puerarin (Pue) has been widely used in the treatment of hypertension and cardiovascular diseases, but the basic mechanism of Pue on myocardial remodeling (MR) of hypertension is not clear. The purpose of this study was to investigate the effect and mechanism of Pue on MR and provide the basis for the clinical application. Thirty male spontaneously hypertensive rats (SHR) and six male Wistar Kyoto rats (WKY) aged 3 months were used in this study, SHR rats were randomly divided into 5 groups, Pue (40 or 80 mg/kg/d, ip) and telmisartan (TELMI) (30 mg/kg/d, ig) were administrated for 12 weeks. We used Echocardiography to detect the cardiac function. Morphology and structure of myocardium were observed. H9C2 cells were subjected to 1 µM Ang Ⅱ in vitro, 100 µM Pue, 0.5 µM Calmodulin-dependent calcineurin (CaN) inhibitor Cyclosporin A (CsA) and 1 µM specific transient receptor potential channel 6 (TRPC6) inhibitor SAR7334 were used in H9C2 cells. Long-term administration of Pue could significantly improve cardiac function, improve morphology and structure of myocardium in vivo. Pue could reduce MR related proteins expression (ACTC1, TGF-ß1, CTGF, ß-MHC and BNP), attenuate ROS, restore MMP and decrease Ca2+-overload in vitro. Further study indicated that Pue could decrease TRPC6 expression and inhibit nuclear factor of activated T cells 3 (NFATc3) nuclear translocation in vitro. These results suggested that puerarin could ameliorate myocardial remodeling through inhibiting TRPC6-CaN-NFATc3 in spontaneously hypertensive rats.


Asunto(s)
Hipertensión , Canales de Potencial de Receptor Transitorio , Animales , Antihipertensivos/uso terapéutico , Calcineurina/metabolismo , Calmodulina/metabolismo , Ciclosporina , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Isoflavonas , Masculino , Miocardio/metabolismo , Factores de Transcripción NFATC , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Especies Reactivas de Oxígeno/metabolismo , Canales Catiónicos TRPC , Canal Catiónico TRPC6/metabolismo , Telmisartán/metabolismo , Telmisartán/uso terapéutico , Factor de Crecimiento Transformador beta1/metabolismo , Canales de Potencial de Receptor Transitorio/metabolismo
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