title: Renal effects of rapamycin in the spontaneously hypertensive rat.
abstract: 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.
authors.affiliation: Inflammation/Bone Metabolism Division, Wyeth-Ayerst Research, Princeton, NJ 08543.
authors.forename: J F
authors.initials: JF
authors.lastname: DiJoseph
authors.forename: M J
authors.initials: MJ
authors.lastname: Mihatsch
authors.forename: S N
authors.initials: SN
authors.lastname: Sehgal
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D011090:Polyenes; D020123:Sirolimus