Angiotensin II as a stimulator of Na +-dependent Ca 2+ efflux from freshly isolated adult rat cardiomyocytes

Abstract

In cardiac tissues, angiotensin II causes inotropic and chronotropic effects on the heart. It is indicated that the mechanism of the inotropic effect of angiotensin II is attributed to an increase in cytosolic free calcium ([Ca 2+] i) in cardiomyocytes. However, increased [Ca 2+] i should be restored to a physiological level because cumulative elevation in [Ca 2+] i leads to irreversible injury in cardiomyocytes. Whereas it is known that angiotensin II causes the increase in [Ca 2+] i in cardiac cells, little is known about the mechanisms of decrease in [Ca 2+] i in cardiomyocytes upon angiotensin II stimulation. In the present study, we examined the effect of angiotensin II on Ca 2+ efflux from freshly isolated adult rat cardiomyocytes. Angiotensin II stimulated the efflux of 45Ca 2+ from the cells in a concentration-dependent manner (10 −7−10 −5 M). The 45Ca 2+ efflux from the cells was inhibited by type 1 angiotensin II receptor inhibitor. The angiotensin II-stimulated 45Ca 2+ efflux was not affected by deprivation of the extracellular Ca 2+, but was dependent on the presence of extracellular Na +. These results indicate that angiotensin II stimulates extracellular Na +-dependent 45Ca 2+ efflux from freshly isolated adult rat cardiomyocytes, probably through its stimulatory effect on the plasma membrane type 1 angiotensin II receptors which may couple to Na + Ca 2+ exchange.