Serum from patients with Raynaud's phenomenon inhibits prostacyclin production.
Prostacyclin (PGI2) and PGE2, the predominant cyclooxygenase products of endothelial cells are potent vasodilators. An inability to produce appropriate concentrations of these prostanoids may be a factor in the pathogenesis of the digital vasospasm experienced by patients with Raynaud's phenomenon (RP). The effect of sera from normal subjects, patients with primary RP, and patients with RP in association with systemic sclerosis (SS) on the production of PGI2 and PGE2 by cultured human endothelial cells was investigated. All sera produced a dose-dependent inhibition of 6-keto-PGF1 alpha, but both the 10% and 20% sera from patients with RP and SS produced a significantly greater inhibition than control sera. The mean production of 6-keto-PGF1 alpha expressed in ng/10(4) cells was 2.278 (normal), 1.9311 (RP), and 2.1824 (SS) after incubation with 1% serum for 24 h. This decreased to 1.3647, 0.5927, and 0.4171, respectively following incubation with 20% sera for 24 h. This represented a 44% (normal), 76% (RP), and 83% (SS) inhibition of 6-keto-PGF1 alpha production compared with serum free media. Similar results were obtained after 1 h incubation experiments. There was a nonsignificant decrease in mean PGE2 production following similar incubations with 1% and 20% sera for 24 h. These results suggest that factor(s) present in the sera of patients with RP may reduce the ability of endothelial cells to synthesize or release the vasodilator and antiaggregatory prostanoid PGI2.
Rustin
M H
MH
Department of Dermatology, Middlesex Hospital, London, U.K.
Bull
H A
HA
Machin
S J
SJ
Koro
O
O
Dowd
P M
PM
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003864:Depression, Chemical; D015232:Dinoprostone; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D011458:Prostaglandins E / Q000096:biosynthesis*; D011928:Raynaud Disease / Q000097:blood* / Q000209:etiology; D012595:Scleroderma, Systemic / Q000097:blood / Q000150:complications
D011458:Prostaglandins E; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D015232:Dinoprostone