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

The aim of the present study was to assess the status of ET-1 receptor subt ypes (ETA and ETB) in ventricular myocytes and fibroblasts and to determine the role of PKC-dependent pathways in ET-1-stimulated cardiac cells in deo xycorticosterone acetate (DOCA)-salt hypertensive rats. Systolic blood pres sure 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 ETA subtype, whereas in fibr oblasts ETA and ETB receptors were present in a 1:3 ratio, In DOCA-salt rat s, the density of the ETA receptor subtype was reduced by 31% in cardiomyoc ytes and in cardiac fibroblasts only ETB receptor density was decreased by 29%. Affinity was unchanged. The relative expression of immunoreactive PKC alpha, gamma and epsilon was significantly increased, whereas PKC delta was not altered in cardiac extracts of DOCA-salt rats. In cardiac fibroblasts from DOCA-salt rats PKC delta was significantly increased and PKC epsilon w as not translocated after ET-1 stimulation. The hearts of DOCA-salt hyperte nsive rats are thus characterized by: (1) decreased density of cardiomyocyt e ETA receptors and fibroblast ETB receptors; (2) cell-specific enhanced ex pression of some PKC isoenzymes (alpha, alpha, delta and epsilon): and (3) unresponsiveness of PKC epsilon to translocate in the presence of ET-1. Tog ether with alterations of ET-1-induced Ca2+ handling in cardiac myocytes an d fibroblasts, which we previously reported, results from the present study indicate a marked modification of the cardiac ET-1 system of DOCA-salt hyp ertensive rats. (C) 2000 Academic Press.