Interaction between nitric oxide and cyclooxygenase pathways in endothelial cells.
Nitric oxide (NO) and cyclooxygenase (COX) derived prostaglandins (PGs) are involved in vascular homeostasis. Contradictory results have been obtained in previous studies on the putative 'cross-talk' between these two pathways. Our aim was to evaluate the interaction between NO and PG release in human microvascular endothelial cells (HMEC-1) and in umbilical vein endothelial cells (HUVEC).


METHODS
Medium samples were assayed for nitrite/nitrate (NO(x)) and L-citrulline levels while lysed cells were assayed for endothelial NO synthase (eNOS), as markers of NO production. Prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) were assessed as indicators of COX activity.


RESULTS
The NO donor sodium nitroprusside and L-arginine increased PGs levels in both cell types. N(G)-monomethyl-L-arginine (L-NMMA) significantly inhibited 6-keto-PGF1alpha release without significantly reducing PGE2)levels. Indomethacin increased both NO(x), eNOS and L-citrulline levels. PGE2 treatment did not modify NO(x) values.


CONCLUSIONS
The stimulation of PGs by NO may represent an additional pathway used by exogenous nitrovasodilators to elicit vasodilation. Reduction of PGs by inhibition of COX was compensated by enhanced NO. Conversely, PGs()did not compensate()decreased NO following L-NMMA treatment. Treatment with the vasodilatator prostaglandin E2 did not modify NO(x) levels.
Institute of Clinical Physiology, CNR, Pisa, Italy. cristina.vassalle@ifc.cnr.it
Cristina
C
Vassalle
Claudio
C
Domenici
Valter
V
Lubrano
Antonio
A
L'Abbate
D001120:Arginine / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011453:Prostaglandins / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin