Role of Endothelium on Cyclopiazonic Acid-induced Vascular Contractions in Rat Aorta

Spacio-temporal changes of intracellular Ca2+ concentrations ([Ca2+]i) are known to play central role in numerous cellular processes such as muscle contraction, gene expression, development, proliferation and apoptosis1. While global increases in [Ca2+]i in vascular smooth muscle cells (VSMCs) elicit contraction2, 3, [Ca2+]i elevation in endothelial cells (ECs) causes vasorelaxation by triggering synthesis and/or release of vasoactive substances including nitric oxide (NO) or prostanoids4, 5. Physiological or pathological stimuli result in elevation of [Ca2+]i via voltage-operated Ca2+ channels (VOCCs), receptor-operated Ca2+ channels (ROCCs) as well as store-operated Ca2+ channels (SOCCs)2, 6, 7. Store-operated Ca2+ entry (SOCE) is activated by depletion of intracellular Ca2+ stores via inositol 1,4,5-triphosphate (IP3) as well as other Ca2+-releasing signals. Ca2+ stores can also be depleted by uncompensated Ca2+ leakage from sarcoplasmic reticulum (SR) that is caused by selective sarcoplasmic-endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitors, cyclopiazonic acid (CPA) and thapsigargin (8, 9), both of which are known to induce SOCE10.