Functional and cellular interactions between nitric oxide and prostacyclin

Nitric oxide (NO) and rostacyclin (PGI(2)) can be released by vascular agen ts to synergize e their effects on vascular relaxation. In the present stud y we assess whether NO could affect PGI(2) production. We evaluated the eff ect of NO on PGI(2)-Mediated arachidonic acid (AA)-induced relaxation in th e perfused heart. We used cultured endothelial cells to characterize the me chanism involved in the NO effect on PGI2 synthesis. AA-induced PGI(2) synt hesis was enhanced when NO synthesis was inhibited. NO inhibited AA-induced relaxation and PGI(2) release in the coronary circulation. S-Nitroso-acety l-DL-penicillamine (SNAP) decreased PGI, production in cultured endothelial cells. The SNAP effect was blunted by the inhibitor of soluble guanylate c yclase (LY-83,583) and the blocker of cGMP-dependent protein kinases (H-9). Specific cyclooxygenase-1 (COX-1) immunoprecipitation was associated to co -precipitation of four proteins. COX-I showed neither serine nor threonine phosphorylation. One of the proteins that co-precipitated with COX-I presen ted increased serine phosphorylation in the presence of SNAP This effect wa s inhibited by the H-9. We suggest that NO, through cGMP-dependent protein kinases, produces the phosphorylation of a 104-kDa protein that is associat ed with inhibition in the activity of the COX-1, decreasing PGI, synthesis and thereby decreasing coronary PGI(2)-mediated vasodilatation. (C) 2001 El sevier Science Inc. All rights reserved.