Effect of angiotensin II on Ca2+ efflux from freshly isolated adult rat cardiomyocytes: possible involvement of Na+/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 45Ca2+ from the cells in a concentration-dependent manner, at least in pharmacological doses of 10(-8) M to 10(-5) M. The 45Ca2+ efflux was inhibited by the type 1 angiotensin II receptor antagonist losartan, but not by the type 2 antagonist PD 123319. Angiotensin II also induced an increase in cytosolic free calcium ([Ca2+]i) and inositol trisphosphate formation within the cardiomyocytes. Angiotensin II-induced 45Ca2+ efflux and the increase in [Ca2+]i were both inhibited by thapsigargin, a specific inhibitor of the sarcoplasmic reticulum Ca2+ pump. The 45Ca2+ efflux was not affected by removal of the extracellular Ca2+ but was dependent on the presence of extracellular Na+. In addition, angiotensin II caused 22Na+ influx into the cells. These results indicate that angiotensin II stimulates Na+-dependent 45Ca2+ efflux from freshly isolated adult rat cardiomyocytes, probably through its stimulatory effect on the plasma membrane type 1 angiotensin II receptors. Angiotensin II-induced increase in [Ca2+]i may cause an activation of Na+/Ca2+ exchange which finally results in the stimulation of 45Ca2+ efflux from the cells. Since it is reported that Na+/Ca2+ exchange is important in calcium homeostasis within the cells, angiotensin II may play some role in the reduction of intracellular Ca2+ from isolated adult rat cardiomyocytes.
Fukuta
Y
Y
Department of Cardiovascular Surgery, School of Medicine, The University of Tokushima, Japan.
Yoshizumi
M
M
Kitagawa
T
T
Hori
T
T
Katoh
I
I
Houchi
H
H
Tamaki
T
T
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D012964:Sodium; D000252:Calcium-Transporting ATPases; D002118:Calcium