EFFECT OF ANGIOTENSIN-II ON CA2-RAT CARDIOMYOCYTES - POSSIBLE INVOLVEMENT OF NA+( EFFLUX FROM FRESHLY ISOLATED ADULT)CA2+ EXCHANGER/

In the present study, we examined the effect of angiotensin II on Ca2 efflux from freshly isolated adult rat cardiomyocytes. Angiotensin II stimulated the efflux of Ca-45(2+) from the cells in a concentration- dependent manner, at least in pharmacological doses of 10(-8) M to 10( -5) M. The Ca-45(2+) efflux was inhibited by the type 1 angiotensin II receptor antagonist losartan, but not by the type 2 antagonist PD 123 319. Angiotensin II also induced an increase in cytosolic free calcium ([Ca2+](i)) and inositol trisphosphate formation within the cardiomyo cytes. Angiotensin II-induced Ca-45(2+) efflux and the increase in [Ca 2+](i) were both inhibited by thapsigargin, a specific inhibitor of th e sarcoplasmic reticulum Ca2+ pump. The Ca-45(2+) efflux was not affec ted by removal of the extracellular Ca2+ but was dependent on the pres ence of extracellular Na+. In addition, angiotensin II caused Na-22(+) influx into the cells. These results indicate that angiotensin II sti mulates Na+-dependent Ca-45(2+) efflux from freshly isolated adult rat cardiomyocytes, probably through its stimulatory effect on the plasma membrane type 1 angiotensin II receptors. Angiotensin II-induced incr ease in [Ca2+](i) may cause an activation of Na+/Ca2+ exchange which f inally results in the stimulation of Ca-45(2+) efflux from the cells. Since it is reported that Na+/Ca2+ exchange is important in calcium ho meostasis within the cells, angiotensin II may play some role in the r eduction of intracellular Ca2+ from isolated adult rat cardiomyocytes. (C) 1998 Elsevier Science Inc.