Tetrandrine inhibits Ca2+ release-activated Ca2+ channels in vascular endothelial cells

The effects of tetrandrine (TET), a Ca2+ antagonist of bis-benzylisoquinoln e alkaloid origin, on cultured single bovine pulmonary artery endothelial c ells were examined using fluorescence ratio imaging and whole-cell attached patch-clamp techniques. Thapsigargin (TSG, 100 nM), a selective endoplasmi c reticulum Ca2+-ATPase pump inhibitor known to induce the release of nitri c oxide (NO) from vascular endothelial cells via a Ca2+-dependent manner, c aused a rapid elevation of cytosolic Ca2+ concentration, which was inhibite d by 30 muM TET. In whole-cell patch-clamp study using the same vascular en dothelial cells, addition of 100 nM TSG caused a significant enhancement of depolarization-evoked Ca2+-dependent, outward K+ currents, which could als o be abolished by 30 muM TET. The present results demonstrate directly that TET, in addition to its known inhibitory effects on vascular smooth muscle by virtue of its Ca2+ antagonistic actions, also inhibits NO production by the endothelial cells through blockade of Ca2+ release-activated Ca2+ chan nels. (C) 2001 Elsevier Science Inc. All rights reserved.