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 the transmembrane ⁴⁵Ca²⁺ 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 investigated. 2. The application of AT-II during steady-state 118 mM K⁺-induced contractions 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 initial rapid and transient increase in [Ca²⁺](i) was abolished, however, neither 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⁺ concentration ([Ba²⁺](i)) level 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 enhanced Ca²⁺ efflux rate induced by 118 mM K⁺-depolarization, whereas AT-II did increase the enhanced ⁴⁵Ca²⁺ influx and the ⁴⁵Ca²⁺ net uptake induced by 118 mM K⁺-depolarization. 6. Pretreatment with calphostin-C, partially, but significantly inhibited the 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.