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

Endothelial cells have a key role in the cardiovascular system. Most endothelial cell functions depend on changes in cytosolic Ca(2+) concentrations (Ca(2+)(i)) to some extent and Ca2+ signalling acts to link external stimuli with the synthesis and release of regulatory factors in endothelial cells. The Ca(2+)(i) is maintained by a well-balanced Ca(2+) flux across the endoplasmic reticulum and plasma membrane. 2. Cyclic nucleotides, such as cAMP and cGMP, are very important second messengers. The cyclic nucleotides can affect Ca(2+)(i) directly or indirectly (via the actions of protein kinase (PK) A or PKG-mediated phosphorylation) by regulating Ca(2+) mobilization and Ca(2+) influx. Fine-tuning of Ca(2+)(i) is also fundamental to protect endothelial cells against damaged caused by the excessive accumulation of Ca(2+). 3. Therapeutic agents that control cAMP and cGMP levels have been used to treat various cardiovascular diseases. 4. The aim of the present review is to discuss: (i) the functions of endothelial cells; (ii) the importance of Ca(2+)(i) in endothelial cells; (iii) the impact of excessive Ca(2+)(i) in endothelial cells; and (iv) the balanced control of Ca(2+)(i) in endothelial cells via involvement of cyclic nucleotides (cAMP and cGMP) and their general effectors.