RENAL EFFECTS OF RAPAMYCIN IN THE SPONTANEOUSLY HYPERTENSIVE RAT

被引：28

作者：

DIJOSEPH, JF

MIHATSCH, MJ

SEHGAL, SN

机构：

[1] Inflammation/Bone Metabolism Division, Wyeth-Ayerst Research, Princeton, 08543, NJ

[2] Institute of Pathology, University of Basel, Basel

来源：

TRANSPLANT INTERNATIONAL | 1994年 / 7卷 / 02期

关键词：

RAPAMYCIN; RAT; RENAL FUNCTION; SPONTANEOUSLY HYPERTENSIVE RAT;

D O I：

10.1007/BF00336467

中图分类号：

R61 [外科手术学];

学科分类号：

摘要：

The effects of rapamycin (RAPA), administered at therapeutic doses, were investigated in the spontaneously hypertensive rat (SHR). Additionally, the reversibility of RAPA's renal effects was investigated at a supratherapeutic dose. At doses that were active in preventing heart and kidney allograft rejection in the rat (0.01-0.08 mg/kg i.v.), RAPA had no effect on kidney function or rat body weight gain. At higher doses (0.8 mg/kg), RAPA produced significant changes in kidney function parameters and caused a loss in body weight. Histopathologic changes, including necrotizing vasculopathy and tubular atrophy, were noted at therapeutic doses. The effects of RAPA on kidney function were completely reversible after a 2-week washout period, though the histopathologic changes were still evident. These studies demonstrate that RAPA does not impair kidney function at therapeutic doses when administered for 2 weeks but does appear to accelerate the naturally occurring renal lesions of the SHR.

引用

页码：83 / 88

页数：6

共 22 条

[11]

Feld L.G., Cachero S., VanLiew J.B., Enalapril and renal injury in spontaneously hypertensive rats, Hypertension, 16, pp. 544-554, (1990)

[12]

Kahan B.D., Chang J.Y., Sehgal S.N., Preclinical evaluation of a new potent immunosuppressive agent, rapamycin, Transplantation, 52, pp. 185-191, (1991)

[13]

Morris R.E., Rapamycins: antifungal, antitumor, antiproliferative and immunosuppressive macrolides, Transplantation Reviews, 6, pp. 39-87, (1992)

[14]

Ryffel B., Mihatsch M.J., Cyclosporin nephrotoxicity, Toxicol Pathol, 14, pp. 73-82, (1986)

[15]

Ryffel B., Siegl H., Petric R., Muller A.M., Hauser R., Mihatsch M.J., Nephrotoxicity of cyclosporin in spontaneously hypertensive rats: effects on blood pressure and vascular lesions, Clin Nephrol, 25, pp. S193-S198, (1986)

[16]

Schreiber S.L., Liu J., Albers M.W., Rosen M.K., Standaert R.F., Wandless T.J., Somers P.K., Molecular recognition of immunophilins and immunophilin-ligand complexes, Tetrahedron, 48, pp. 2545-2558, (1992)

[17]

Stepkowski S.M., Goto S., Ito T., Reynolds K., Didlake R., Kim E.K., Kahan B.D., Prolongation of heterotopic heart allograft survival by local delivery of continuous low-dose cyclosporin therapy, Transplantation, 47, pp. 17-23, (1989)

[18]

Stepkowski S.M., Chen H., Daloze P., Kahan B.D., Prolongation by rapamycin of heart, kidney, pancreas, and small bowel allograft survival in rats, Transplant Proc, 23, pp. 507-508, (1991)

[19]

Stepkowski S.M., Chen H., Daloze P., Kahan B.D., Rapamycin, a potent immunosuppressive drug for vascularized heart, kidney, and small bowel transplantation in the rat, Transplantation, 51, pp. 22-26, (1991)

[20]

Whiting P.H., Adam B.J., Woo J., Hasan N.U., Thoon A.W., The effect of rapamycin on renal function in the rat: a comparative study with cyclosporin, Toxicol Lett, 58, pp. 169-179, (1991)

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