Fig. 3.

Regulation of endothelial and VSM [Ca²⁺]_i during Norm-Preg and preeclampsia. Norm-Preg is associated with increased expression and Ca²⁺-dependent activation of endothelial eNOS and COX, leading to increased NO and PGI₂ production. NO and PGI₂ act on VSM, causing an increase in cGMP and cAMP, which activate Ca²⁺ extrusion and VSM relaxation mechanisms. Increased EDHF during pregnancy causes VSM hyperpolarization, and inhibition of Ca²⁺ entry through voltage-gated channels. In preeclampsia, a decreased NO bioavailability mainly due to increased ROS would cause reduction of VSM relaxation. Also, the release of bioactive factors such as cytokines from the placenta and other sources causes an increase in the release of endothelium-derived contracting factors such as ET-1 and TXA₂ and AngII which in turn cause an increase in VSM [Ca²⁺]_i and the Ca²⁺-sensitization pathways such as PKC and Rho-kinase, leading to enhanced vasoconstriction, increased vascular resistance and BP.