Renal effects of rapamycin in the spontaneously hypertensive rat.
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.
DiJoseph
J F
JF
Inflammation/Bone Metabolism Division, Wyeth-Ayerst Research, Princeton, NJ 08543.
Mihatsch
M J
MJ
Sehgal
S N
SN
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011090:Polyenes / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011918:Rats, Inbred SHR; D020123:Sirolimus
D007166:Immunosuppressive Agents; D011090:Polyenes; D020123:Sirolimus