ROLE OF CYCLIC NUCLEOTIDES IN THE CONTROL OF CYTOSOLIC Ca2+ LEVELS IN VASCULAR ENDOTHELIAL CELLS

P>Endothelial cells have a key role in the cardiovascular system. Most endothelial cell functions depend on changes in cytosolic Ca2+ concentrations ([Ca2+](i)) to some extent and Ca2+ signalling acts to link external stimuli with the synthesis and release of regulatory factors in endothelial cells. The [Ca2+](i) is maintained by a well-balanced Ca2+ flux across the endoplasmic reticulum and plasma membrane. Cyclic nucleotides, such as cAMP and cGMP, are very important second messengers. The cyclic nucleotides can affect [Ca2+](i) directly or indirectly (via the actions of protein kinase (PK) A or PKG-mediated phosphorylation) by regulating Ca2+ mobilization and Ca2+ influx. Fine-tuning of [Ca2+](i) is also fundamental to protect endothelial cells against damaged caused by the excessive accumulation of Ca2+. Therapeutic agents that control cAMP and cGMP levels have been used to treat various cardiovascular diseases. The aim of the present review is to discuss: (i) the functions of endothelial cells; (ii) the importance of [Ca2+](i) in endothelial cells; (iii) the impact of excessive [Ca2+](i) in endothelial cells; and (iv) the balanced control of [Ca2+](i) in endothelial cells via involvement of cyclic nucleotides (cAMP and cGMP) and their general effectors.