Retardation of renal growth and ornithine decarboxylase activity by cyclosporine after uninephrectomy in rats.
Renal transplantation or a partial reduction in renal mass prompts compensatory growth of the kidney, an event that appears to be stimulated by a circulating substance, the purported renotropic factor. This factor may stimulate synthesis of renal polyamines by induction of the rate-limiting enzyme in polyamine metabolism, ornithine decarboxylase. Cyclosporine has been shown to attenuate induction of renal ornithine decarboxylase activity in response to other tropic hormones, such as prolactin, thyroxine, and dexamethasone. These studies were undertaken to evaluate the effects of cyclosporine on induction of renal ornithine decarboxylase activity and growth in response to the serum renotropic factor. Rats were given either 15.0 or 25.0 mg/kg/day or cyclosporine for six days following removal of one kidney. The growth of the remaining kidney was reduced by cyclosporine treatment compared with pair-fed, vehicle-treated control animals. Administration of 25.0 mg/kg/day of cyclosporine also reduced the activity of ornithine decarboxylase in the growing kidney. We conclude that cyclosporine imposes a limitation on the ability of the kidney to grow in response to a reduction in renal mass in rats. The mechanisms of this effect may relate to a blunting of the induction of renal ornithine decarboxylase activity in response to the renotropic factor.
Logan
J L
JL
Renal Section, V.A. Medical Center, Tucson, AZ 85723.
Benson
B
B
D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D003864:Depression, Chemical; D007668:Kidney / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D009392:Nephrectomy; D009955:Ornithine Decarboxylase / Q000032:analysis*; D011073:Polyamines / Q000096:biosynthesis / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins; D011073:Polyamines; D009955:Ornithine Decarboxylase