Nephrology Dialysis Transplantation, Vol 14, Issue 6 1376-1384, Copyright © 1999 by Oxford University Press
H Murakami, K Yayama, J Chao and L Chao
Background: Atrial natriuretic peptide (ANP) is a
cardiac hormone which exerts potent natriuretic and vasorelaxant
activities. The aim of this study is to investigate potential protective
effects of ANP gene delivery in gentamycin-induced nephrotoxicity.
Methods: Adenovirus (Ad.RSV-ANP) carrying the human
ANP gene or carrying the LacZ gene (Ad.RSV-LacZ) under the control of the
Rous sarcoma virus promoter were delivered intravenously on the first day
of gentamycin administration. Sprague-Dawley rats were injected
subcutaneously with gentamycin daily for 10 days.
Results: A single systemic injection of Ad.RSV-ANP at
a dose of 1.2 x 1010 pfu results in a significant
increase in urine excretion, water intake, urinary sodium and potassium
excretion. Adenovirus-mediated ANP gene delivery significantly increased
renal blood flow, glomerular filtration rates and urine flow as well as
attenuated the elevation of blood urea nitrogen levels. Histological
evaluations revealed that ANP delivery attenuated gentamycin-induced renal
tubular damage, cellular necrosis, and lumenal protein casts. The
expression of human ANP mRNA was identified in rat kidney, heart, aorta and
liver. Immunoreactive human ANP was detected in the heart and kidney of
rats injected with Ad.RSV-ANP but not in rats injected with Ad.RSV-LacZ.
Cyclic GMP levels in the kidney were significantly increased in rats
receiving ANP gene delivery. Conclusions: This study
shows that ANP gene delivery exhibits protection against gentamycin-induced
nephrotoxicity and raises the potential to use ANP gene therapy for the
treatment of drug-induced renal failure. Key words:
adenovirus; atrial natriuretic peptide; gene delivery; gentamycin;
nephrotoxicity
ORIGINAL ARTICLES
Atrial natriuretic peptide gene delivery attenuates gentamycin-induced nephrotoxicity in rats
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425-2211, USA; Corresponding author
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