Increased prostacyclin production from human veins by dipyridamole: an in vitro and ex vivo study.
The effect of dipyridamole on prostacyclin (PGI2) production in the presence or in the absence of sodium arachidonate was examined in human veins collected from otherwise normal subjects undergoing saphenous vein removal. Vein segments, maintained in ex vivo culture, that were removed from subjects treated with dipyridamole for two days prior to surgery synthesized 2.5 times more PGI2 (p less than 0.05) than veins that were removed from placebo-treated subjects when incubated in the presence of arachidonate. This difference decreased progressively when vein segments were washed repeatedly and then re-incubated in the presence of arachidonate. Direct addition of dipyridamole to vein segments incubated in vitro resulted in a dose-dependent increase in PGI2 production when the incubation was carried out in the presence of arachidonic acid. No effect of dipyridamole was observed in experiments performed in the absence of arachidonic acid. A mathematical analysis based on both ex vivo and in vitro experiments of the rate of decline of endothelial cell PGI2 biosynthesis suggested that the elevation of PGI2 with dipyridamole treatment resulted from increased PGI2 synthesis rather than decreased PGI2 catabolism. These data support the hypothesis that dipyridamole both ex vivo and in vitro enhances and prolongs PGI2 production by human vessels.
Costantini
V
V
Istituto di Semeiotica Medica, Università di Perugia, Italy.
Talpacci
A
A
Bastiano
M L
ML
Boschetti
E
E
Cipolloni
S
S
Bisacci
R
R
Nenci
G G
GG
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology*; D004357:Drug Synergism; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D013268:Stimulation, Chemical; D014680:Veins / Q000187:drug effects* / Q000378:metabolism
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D004176:Dipyridamole; D011464:Epoprostenol