Regulation mechanism for the enhancement of PGI2 generation by nitroglycerine

Previously we reported that nitroglycerine (NTG) enhances the PGI2 generation via activation of phospholipase A2 of arachidonic acid cascade in the cultured human vascular endothelial cells. This paper reports the effects of NTG on the PGI2 generation with reference to cyclic nucleotide metabolism. In the presence of MIX, intracellular cAMP or cGMP level was increased and PGI2 generation of the endothelial cells was decreased. Addition of NTG had no effect on the level of intracellular cAMP in this experimental system, while cGMP was increased 1.21 folds by NTG. Addition of dibutyryl CAMP or 8-bromo cGMP increased intracellular cAMP or cGMP and diminished PGI2 generation. Addition of exogenous PGI2 caused the increase of intracellular cAMP level without affecting cGMP level. Through these experiments, it is speculated that enhancement of PGI2 generation is regulated by increased CAMP due to increased PGI2, that is negative feedback mechanism of PGI2 generation, and that increase of cGMP level by NTG may also regulate PGI2 generation.