The effect of tacrolimus (FK506) and cyclosporin A (CyA) on peripheral serotonergic mechanisms in uremic rats.
The aim of this study was to investigate the mechanism of hypertension and thromboembolic events induced by cyclosporin (CyA) and tacrolimus (FK506) in respect to their action on the serotonergic blood system. The study was carried out on healthy rats and those with experimental chronic renal failure. CyA injected into healthy and uremic rats caused an increase in serotonin (5-HT) concentration levels in whole blood and platelets. Concomitantly a rise in systolic blood pressure was observed. Platelet aggregation values were significantly higher in uremic rats given CyA. FK506 had no influence on 5-HT blood content, blood pressure or platelet aggregation values. It is concluded that 5-HT may play a role in the development of hypertension and thrombotic events caused by CyA. Furthermore, lower incidence of these complications during FK506 treatment could be the result of this drug's limited effect on the serotonergic blood system.
Mysliwiec
J
J
Department of Pharmacodynamics, Medical School, Bialystok, Poland.
Azzadin
A
A
Chabielska
E
E
Takada
A
A
Mysliwiec
M
M
Buczko
W
W
D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood / Q000139:chemically induced*; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood*; D016559:Tacrolimus / Q000009:adverse effects* / Q000627:therapeutic use; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced*; D014511:Uremia / Q000097:blood / Q000188:drug therapy*
D007166:Immunosuppressive Agents; D012701:Serotonin; D016572:Cyclosporine; D016559:Tacrolimus