Altered Cardiac Endothelin Receptors and Protein Kinase C in Deoxycorticosterone-Salt Hypertensive Rats

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.