Endothelin-1 signaling is altered in cardiac cells from deoxycorticosterone acetate-salt hypertensive rats.
The cardiac cellular effects of endothelin-1 (ET-1) on intracellular free Ca2+ concentration ([Ca2+]i) were investigated in deoxycorticosterone acetate (DOCA)-salt rats with severe cardiac hypertrophy. [Ca2+]i was measured by fura-2 methodology in ventricular cardiomyocytes and fibroblasts of DOCA-salt hypertensive and control unilaterally nephrectomized rats (Uni-Nx). Blood pressure and heart weight were increased (p < 0.01) in DOCA-salt rats compared to control rats. ET-1 (10(-12)-10(-6) M) increased [Ca2+]i in a dose-dependent manner in both cell types from control and hypertensive rats. However, ET-1-induced [Ca2+]i responses were significantly attenuated (p < 0.01) in cardiomyocytes and fibroblasts of DOCA-salt rats. Sarafotoxin S6c (S6c) increased [Ca2+]i in fibroblasts but not in cardiomyocytes. In conclusion, ET-1 dose-dependently increased [Ca2+]i in cardiomyocytes (primarily via ETA receptors) and fibroblasts (via ETA and ETB receptors). Cardiac cell ET-1 signaling pathways are blunted in DOCA-salt hypertensive rats. ET-1 may not play a critical role in the pathophysiology of the severe concentric cardiac hypertrophy present in DOCA-salt hypertensive rats.
Touyz
R M
RM
Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
Fareh
J
J
Thibault
G
G
Schiffrin
E L
EL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology; D002478:Cells, Cultured; D003900:Desoxycorticosterone; D019332:Endothelin-1 / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D012965:Sodium Chloride
D019332:Endothelin-1; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D002118:Calcium