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

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Abstract
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. 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. 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. 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. 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. Pretreatment with calphostin‐C, partially, but significantly inhibited the decrease in [Ca2+]i induced by AT‐II. 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. British Journal of Pharmacology (2000) 129, 437–447; doi:10.1038/sj.bjp.0703093