Altered cardiac endothelin receptors and protein kinase C in deoxycorticosterone-salt hypertensive rats

Fareh, J., Touyz, R.M. , Schiffrin, E.L. and Thibault, G. (2000) Altered cardiac endothelin receptors and protein kinase C in deoxycorticosterone-salt hypertensive rats. Journal of Molecular and Cellular Cardiology, 32(4), pp. 665-676. (doi:10.1006/jmcc.2000.1110)

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Abstract

J. Fareh, R. M. Touyz, E. L. Schiffrin and G. Thibault. Altered Cardiac Endothelin Receptors and Protein Kinase C in Deoxycorticosterone-Salt Hypertensive Rats. Journal of Molecular and Cellular Cardiology (2000) 32, 665–676. The aim of the present study was to assess the status of ET-1 receptor subtypes (ETAand ETB) in ventricular myocytes and fibroblasts and to determine the role of PKC-dependent pathways in ET-1-stimulated cardiac cells in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Systolic blood pressure and relative heart to body weight were significantly increased in DOCA-salt rats. In unilaterally nephrectomized (Uni-Nx) control rats, more than 90% of cardiomyocyte ET receptors were of the ETAsubtype, whereas in fibroblasts ETAand ETBreceptors were present in a 1:3 ratio. In DOCA-salt rats, the density of the ETAreceptor subtype was reduced by 31% in cardiomyocytes and in cardiac fibroblasts only ETBreceptor density was decreased by 29%. Affinity was unchanged. The relative expression of immunoreactive PKC α, γ and ϵ was significantly increased, whereas PKC δ was not altered in cardiac extracts of DOCA-salt rats. In cardiac fibroblasts from DOCA-salt rats PKCδ was significantly increased and PKC ϵ was not translocated after ET-1 stimulation. The hearts of DOCA-salt hypertensive rats are thus characterized by: (1) decreased density of cardiomyocyte ETAreceptors and fibroblast ETBreceptors; (2) cell-specific enhanced expression of some PKC isoenzymes (α, γ,δ and ϵ); and (3) unresponsiveness of PKC ϵ to translocate in the presence of ET-1. Together with alterations of ET-1-induced Ca2+handling in cardiac myocytes and fibroblasts, which we previously reported, results from the present study indicate a marked modification of the cardiac ET-1 system of DOCA-salt hypertensive rats.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Fareh, J., Touyz, R.M., Schiffrin, E.L., and Thibault, G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Molecular and Cellular Cardiology
Publisher:Elsevier
ISSN:0022-2828

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