Nitric oxide modulates endothelin 1-induced Ca2+ mobilization and cytoskeletal F-actin filaments in human cerebromicrovascular endothelial cells

A functional interrelation between nitric oxide (NO), the endothelial-deriv ed vasodilating factor, and endothelin 1 (ET-1), the potent vasoconstrictiv e peptide, was investigated in microvascular endothelium of human brain. No r-1 dose-dependently decreased the ET-l-stimulated mobilization of Ca2+. Th is response was mimicked with cGMP and abrogated by inhibitors of guanylyl cyclase or cGMP-dependent protein kinase G. These findings indicate that NO and ET-I interactions involved in modulation of intracellular Ca2+ are med iated by cGMP/protein kinase G. In addition, Nor-1-mediated effects were as sociated with rearrangements of cytoskeleton F-actin filaments. The results suggest mechanisms by which NO-ET-1 interactions may contribute to regulat ion of microvascular function.