Comparison of the effect of rapamycin and FK506 on release of prostacyclin and endothelin in vitro.
Alterations in mesangial and endothelial cell production of vasoactive substances may be a contributing factor to the decreased renal blood flow and glomerular thrombosis associated with FK506 nephrotoxicity. In preliminary studies Rapamycin (RAPA) appears to induce fewer renal side-effects than FK506, although further documentation is required. In this study, the effects of FK506 and RAPA on release of prostacyclin, a vasodilator, and endothelin, a vasoconstrictor, were investigated in cultured rabbit mesangial and endothelial cells. In general, the effects of both RAPA and FK506 on the basal or stimulated release of prostacyclin (as measured by release of its stable metabolite, 6-keto-PGF1 alpha) or endothelin from mesangial cells and endothelial cells were similar with the following exceptions: RAPA resulted in a significant (p < 0.05) increase in the release of prostacyclin (PGI2) from endothelial cells, while in contrast, FK506 resulted in a significant decrease in the release of this analyte from these cells. The similar effects both drugs have on release of vasodilatory and vasoconstrictor substances in vitro does not explain the differences in renal side-effects of the drugs in vivo.
Yatscoff
R W
RW
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.
Fryer
J
J
Thliveris
J A
JA
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D016718:Arachidonic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011090:Polyenes / Q000633:toxicity*; D011817:Rabbits; D020123:Sirolimus; D016559:Tacrolimus / Q000633:toxicity*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000935:Antifungal Agents; D016232:Endothelins; D011090:Polyenes; D016212:Transforming Growth Factor beta; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D020123:Sirolimus; D016559:Tacrolimus