The α1D-adrenoreceptor antagonist BMY 7378 reverses cardiac hypertrophy in spontaneously hypertensive rats.

Rodríguez, J. E. et al. (2020) The α1D-adrenoreceptor antagonist BMY 7378 reverses cardiac hypertrophy in spontaneously hypertensive rats. Journal of Hypertension, 38(8), pp. 1496-1503. (doi: 10.1097/HJH.0000000000002412) (PMID:32195823)

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Objective: The α1D-adrenoreceptor (α1D-AR) is involved in angiotensin II-induced vascular remodeling and hypertension. Whether α1D-AR plays a role in hypertension-associated cardiac hypertrophy is unclear. Here we investigated effects of BMY 7378, a selective α1D-AR antagonist, on cardiac status in aged spontaneously hypertensive rats (SHR). Methods: Male SHR were studied during the phase of developing hypertension (5 and 10 weeks old) and once hypertension was established (20 and 30 weeks old) to assess the evolution of cardiac hypertrophy. Age-matched WKY rats were studied as controls. Thirty-week-old SHR were treated for 4 weeks with BMY 7378 (10 mg/kg per day, o.a.), or captopril (angiotensin-converting enzyme inhibitor, 40 mg/kg per day, o.a.) (as a positive control). Blood pressure and cardiac function were measured in vivo, cardiac hypertrophy by histology, and α1D-AR protein expression by immunofluorescence. Results: By 30 weeks of age, SHR exhibited significant hypertension and cardiac hypertrophy. BMY 7378 and captopril decreased blood pressure and improved hemodynamic parameters and cardiac function in treated SHR vs. untreated SHR (P < 0.05). Histology showed increased cardiomyocyte size, fibrosis, and left ventricular hypertrophy in SHR hearts. BMY 7378 ameliorated fibrosis and cardiac hypertrophy, but had no effect on cardiomyocyte size in SHR. Effects of BMY 7378 were associated with increased α1D-AR protein expression in SHR. Conclusion: Our data indicate that pharmacological antagonism of α1D-AR reduces blood pressure and associated cardiac hypertrophy in aged SHR. These findings suggest that the α1D-AR plays a pathophysiological role in the development of hypertension and cardiac target organ damage in SHR.

Item Type:Articles
Additional Information:This work was supported by grants IN223519 (RV-M), IN226819 and IN219915 (IAG-O), from PAPIIT, DGAPA, UNAM and Fundacio´n Miguel Alema´n (IAG-O).
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Rodríguez, J. E., Saucedo-Campos, A. D., Vega, A. V., Ramírez-Hernández, D., Martínez-Aguilar, L., Jiménez-Flores, J. R., Andrade-Jorge, E., Estrada-Soto, S. E., Villalobos-Molina, R., Touyz, R. M., and Gallardo-Ortíz, I. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Hypertension
Publisher:Lippincott Williams & Wilkins
ISSN (Online):1473-5598
Copyright Holders:Copyright © 2020 Wolters Kluwer Health, Inc
First Published:First published in Journal of Hypertension 38(8):1496-1503
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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