Role of cyclic nucleotides in the control of cytosolic ca²⁺ levels in vascular endothelial cells: Invited review

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 Ca ²⁺ 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.