Nitric oxide but not prostacyclin is an autocrine endothelial mediator

Using porcine aortic endothelial cells, the present study investigates whether stimulation of prostacyclin (PGI 2) and nitric oxide also causes elevation of the respective second messengers cAMP and cGMP in the endothelial generator cells. The calcium ionophore A23187 at 0.3−3 μM increased endothelial cGMP levels up to 27-fold in an l-arginine-dependent manner as assessed through complete inhibition by N G-monomethyl- l-arginine (100μM). The 36-fold PGI 2 stimulation by 3μM A23187 was not accompanied by an intracellular increase in cAMP or an enhanced cAMP efflux. Correspondingly, the PGI 2 mimetic iloprost (10 pM−100 μM) did not change endothelial cAMP levels. However, forskolin (1−100 μM) and prostaglandin E 2 (PGE 2) (0.1−10 μM) produced concentration-dependent increases in cAMP with a 9-fold and 8-fold stimulation at 100 μM forskolin and 10μM PGE 2, respectively. These results demonstrate that in contrast to NO, PGI 2 acts as a strictly paracrine hormone without affecting the respective second messenger cAMP in the endothelial generator cells.