PMID: 8587392Jan 1, 1995Paper

Effect of FK 506 on the expression of endothelin receptor mRNA in the vasculature

Journal of Cardiovascular Pharmacology
Y TakedaH Mabuchi

Abstract

Tacrolimus (FK 506) is a new, more powerful immunosuppressant and is more effective in the prevention and treatment of allograft rejection in humans than cyclosporine (CysA). The present study was conducted to determine whether FK 506 increases ET(A) receptor mRNA in blood vessels in rats. FK 506 5 mg/kg/day for 4 weeks increased blood pressure and expression of ET(A) receptor mRNA in mesenteric arteries of Wistar-Kyoto rats. However, 0.5 mg/kg/day of FK 506 did not increase blood pressure or ET(A) mRNA levels in the vasculature. The dose of 0.1 microM CysA used in clinical practice induced expression of ET(A) receptor mRNA in cultured rat vascular smooth-muscle cells (VSMCs). A clinical dose (0.01 microM) of FK 506 did not increase expression of ET(A) receptor mRNA in VSMCs. However, 0.1 microM FK 506 increased the levels of ET(A) receptor mRNA in VSMCs. These results indicate that the upregulating effect of FK 506 on the ET(A) receptor in the vasculature may contribute to the genesis of FK 506-induced hypertension. The lower incidence of complications seen with FK 506 may be due in part to its use at a lower clinical dose compared to that of CysA.

Citations

Mar 17, 2000·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·D B CarrT R Easterling
Apr 29, 2000·Current Opinion in Urology·A R Rosenkranz, G Mayer

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