Effects of NO-donors, SIN-1 and GEA 3175 on prostacyclin and cGMP synthesis in cultured rat endothelial cells.
The aim of the present study was to investigate, whether nitric oxide (NO) modifies prostacyclin synthesis in endothelial cells. Two different NO-donors: SIN-1 (3-morpholino sydnonimine) and GEA 3175 (4-aryl-substituted oxatriazol derivative), and the NO-synthesis inhibitor; L-NAME were used. Endothelial cells were incubated with the tested compounds with or without Ca ionophore A23187 stimulation. SIN-1 (> 33 microM) and GEA 3175 (> 1 microM) increased the endothelial cGMP levels independently of A23187 stimulation. SIN-1 did not influence prostacyclin synthesis. GEA 3175 (> 33 microM) increased prostacyclin synthesis up to 2-fold, when incubated without A23187. GEA 3175 with A23187 induced about 30% inhibition in prostacyclin synthesis. L-NAME decreased unstimulated prostacyclin synthesis and this inhibition was reversed by GEA 3175. Obviously NO is able to modulate prostacyclin synthesis, however, much higher concentrations are needed than those to increase cGMP synthesis.
Alanko
J
J
Department of Biomedical Sciences, University of Tampere, FIN.
Sievi
E
E
Lähteenmäki
T
T
Mucha
I
I
Riutta
A
A
Vapaatalo
H
H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects; D006152:Cyclic GMP / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014230:Triazoles / Q000494:pharmacology*
C093084:GEA 3175; D014230:Triazoles; D009569:Nitric Oxide; D000001:Calcimycin; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D011464:Epoprostenol; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester