Functional and cellular interactions between nitric oxide and prostacyclin

Nitric oxide (NO) and rostacyclin (PGI(2)) can be released by vascular agents to synergize e their effects on vascular relaxation. In the present study we assess whether NO could affect PGI(2) production. We evaluated the effect of NO on PGI(2)-Mediated arachidonic acid (AA)-induced relaxation in the perfused heart. We used cultured endothelial cells to characterize the mechanism involved in the NO effect on PGI2 synthesis. AA-induced PGI(2) synthesis was enhanced when NO synthesis was inhibited. NO inhibited AA-induced relaxation and PGI(2) release in the coronary circulation. S-Nitroso-acetyl-DL-penicillamine (SNAP) decreased PGI, production in cultured endothelial cells. The SNAP effect was blunted by the inhibitor of soluble guanylate cyclase (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 presented increased serine phosphorylation in the presence of SNAP This effect was inhibited by the H-9. We suggest that NO, through cGMP-dependent protein kinases, produces the phosphorylation of a 104-kDa protein that is associated with inhibition in the activity of the COX-1, decreasing PGI, synthesis and thereby decreasing coronary PGI(2)-mediated vasodilatation. (C) 2001 Elsevier Science Inc. All rights reserved.