Renal effects of rapamycin in the spontaneously hypertensive rat |
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Authors: | John F DiJoseph Michael J Mihatsch Suren N Sehgal |
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Institution: | (1) Inflammation/Bone Metabolism Division, Wyeth-Ayerst Research, CN 8000, 08543 Princeton, NJ, USA;(2) Institute of Pathology, University of Basel, CH-4003 Basel, Switzerland |
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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. |
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Keywords: | Rapamycin rat renal function Renal function rapamycin rat Spontaneously hypertensive rat rapamycin |
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