Partial isolation and function of the prostacyclin regulating plasma factor.
Rat aortic rings stop producing prostacyclin upon prolonged washing in buffer. This 'exhaustion' is caused by inhibition of cyclo-oxygenase, since these rings still convert cyclic endoperoxides but not arachidonic acid into prostacyclin, and most probably is due to high concentrations of peroxides: it can be accelerated by H2O2 or by interrupting the glutathione cycle, while it is delayed by reduced glutathione. Incubation of exhausted rings in human plasma or in a plasma filtrate restores to some extent prostacyclin formation. This filtrate, in particular from uraemic subjects, also inhibits the H2O2 initiated oxidation of guaiacol by ram seminal vesicle microsomes or horseradish peroxidase. The prostacyclin regulating plasma factor has been partially purified and identified as a stable and very polar molecule of mol. wt. 300-400, able to reactivate prostacyclin generation by exhausted rings. We suggest that one or more low mol. wt. plasma components prolong vascular prostacyclin formation by acting as reducing cofactor for cyclo-oxygenase peroxidase. The main physiological role of this plasma activity is probably to protect the vascular prostacyclin forming system from exhaustion during persistent irritation.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors; D011464:Epoprostenol / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D006139:Guaiacol / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D014462:Ultrafiltration; D014511:Uremia / Q000097:blood
D016861:Cyclooxygenase Inhibitors; D015121:6-Ketoprostaglandin F1 alpha; D006139:Guaiacol; D006861:Hydrogen Peroxide; D011464:Epoprostenol