The mechanism of the decrease in cytosolic Ca2+ concentrations induced by angiotensin II in the high K+-depolarized rabbit femoral artery

1 Using front-surface fluorometry of fura-2-loaded strips, and measuring th e transmembrane Ca-45(2+) fluxes of ring preparations of the rabbit femoral artery, the mechanism underlying a sustained decrease in the cytosolic Ca2 + concentration ([Ca2+](i)) induced by angiotensin II (AT-II) was investiga ted. 2 The application of AT-II during steady-state 118 mM K+-induced contractio ns caused a sustained decrease in [Ca2+](i) following a rapid and transient increase in [Ca2+](i), while the tension was transiently enhanced. 3 When the intracellular Ca2+ stores were depleted by thapsigargin, the ini tial rapid and transient increase in [Ca2+](i) was abolished, however, neit her the sustained decrease in [Ca2+](i) nor the enhancement of tension were affected. 4 Depolarization with 118 mM K+ physiological salt solution containing 1.25 mM Ba2+ induced a sustained increase in both the cytosolic Ba2+ concentrat ion ([Ba2+](i)) lever and tension. However, the application of 10(-6) M AT- II during sustained Ba2+-contractions was found to have no effect on [Ba2+] (i), but it did enhance tension. 5 After thapsigargin treatment, AT-II neither decreased nor increased the e nhanced Ca2+ efflux rate induced by 118 mM K+-depolarization, whereas AT-II did increase the enhanced Ca-45(2+) influx and the Ca-45(2+) net uptake in duced by 118 mM K+-depolarization. 6 Pretreatment with calphostin-C, partially, but significantly inhibited th e decrease in [Ca2+](i) induced by AT-II. 7 These findings therefore suggest that AT-II stimulates Ca2+ sequestration into the thapsigargin-insensitive Ca2+ stores, and thus induces a decrease in [Ca2+](i) in the high external K+-stimulated rabbit femoral artery.