A synthetic analogue of vitamin D3, 22-oxa-1,25-dihydroxy-vitamin D3, stimulates the production of prostacyclin by vascular tissues.
We investigated the effect of 22-oxa-1,25-dihydroxyvitamin D3, a synthetic analogue of vitamin D3, on the production of prostacyclin by vascular tissues using rat aortic rings and A7r5 cells derived from fetal rat aortic smooth muscle. Prostacyclin synthesis by aortic rings of rats treated with 22-oxa-1,25-dihydroxyvitamin D3 was much higher than that of non-treated controls, but did not cause any significant hypercalcemia. Treatment with 22-oxa-1,25-dihydroxyvitamin D3 significantly increased the production of prostacyclin by A7r5 cells for 48 hours in a dose-dependent manner. In time-course studies, cells incubated with 22-oxa-1,25-dihydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 produced prostacyclin progressively over a period of 48 hours. The shortest period of incubation that produced a significant amount of prostacyclin compared with control cultures was 24 hours. We observed that treatment with 22-oxa-1,25-dihydroxyvitamin D3 induced cyclooxygenase mRNA in A7r5 cells. Our data suggest that 22-oxa-1,25-dihydroxyvitamin D3 may possibly be a protective substance against the development of atherosclerosis by modulating prostaglandin metabolism.
Inoue
M
M
Third Department of Internal Medicine, University of Yamanashi Medical School, Japan.
Wakasugi
M
M
Wakao
R
R
Gan
N
N
Tawata
M
M
Nishii
Y
Y
Onaya
T
T
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D011464:Epoprostenol / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D012333:RNA, Messenger; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D002117:Calcitriol; C051883:maxacalcitol