Renal Blood Flow and Serotonin Metabolism in Tacrolimus Treated Rats

Background: Serotonin (5-HT) is a potent vasoconstrictor and activator of platelets, endothelial cells and vascular smooth muscle cells. The result of activation by serotonin is platelet aggregation and vasoconstriction. The aim of the present study was to evaluate the role of serotonin metabolism as a mediator of tacrolimus (FK 506) nephrotoxicity.
Methods: The whole blood and plasma levels of serotonin and its major metabolite (5-hydroxyindoleacetic acid: 5-HIAA) as well as renal cortical blood flow were investigated in rats administered FK 506 at doses of 4, 6 or 8mg/kg b.w. for 14 consecutive days.
Results: Renal cortical blood flow declined in a dose-dependent manner in the rats given FK 506, whereas serum creatinine remained unaltered following FK 506 administration. Although there was no significant change in serotonin, the whole blood and plasma 5-HIAA levels increased significantly following FK 506 administration.
Conclusion: FK 506 may cause acute nephrotoxicity by decreasing renal blood flow and the increase of 5-HIAA suggests some role of serotonin metabolism in the development of FK 506 nephrotoxicity.