EFFECT OF SOME CYCLOOXYGENASE INHIBITORS ON THE INCREASE IN GUANOSINE3' 5'-CYCLIC MONOPHOSPHATE INDUCED BY NO-DONORS IN HUMAN WHOLE PLATELETS/

1 The effect of the NSAIDS indomethacin, indoprofen, diclofenac and ac etylsalicylic acid on the increase in guanosine 3':5'-cyclic monophosp hate (cyclic GMP) induced by nitric oxide-donor agents was tested in h uman whole platelets and in platelet crude homogenate. 2 In whole plat elets, indomethacin reduced the increase in cyclic GMP induced by the nitric oxide-donors (NO-donors) sodium nitroprusside (NaNP) and S-nitr oso-N-acetylpenicillamine (SNAP) in a dose-dependent way, its IC50 bei ng 13.7 mu M and 15.8 mu M, respectively. 3 Of the other cyclooxygenas e inhibitors tested, only indoprofen reduced the increase in cyclic GM P induced by both NO-donors in a dose-dependent way (IC50=32.7 mu M, N aNP and 25.0 mu M, SNAP), while acetylsalicylic acid (up to 1000 mu M) and diclofenac (up to 100 mu M) were ineffective. 4 However, in plate let crude homogenate neither indomethacin nor indoprofen reduced the c yclic GMP production. 5 Indomethacin (10 mu M), indoprofen (30 mu M), diclofenac (100 mu M) and acetylsalicylic acid (1000 mu M) showed a co mparable efficacy in inhibiting platelet thromboxane B-2 (TXB2) produc tion, suggesting that the inhibitory effect of indomethacin and indopr ofen on the increase in cyclic GMP induced by both NO-donors was not m ediated by inhibition of cyclooxygenase. 6 In vitro, the NSAIDs analys ed did not interfere with nitrite production of SNAP. 7 The unhomogene ous behaviour of NSAIDs on the increase in cyclic GMP induced by NO-do nors in whole platelets may contribute to the different pharmacologica l and toxicological characteristics of the drugs, providing new knowle dge on the effect of indomethacin and indoprofen.