[Effect of recombinant atrial natriuretic peptide (r-ANP) on ischemic and cyclosporine-induced kidney damage in rats].
Cyclosporine A (CYA) a new immunosuppressive drug, has greatly improved the outcome of solid graft transplantation. The nephrotoxicity of CYA, however, is a serious problem, and constitutes the major obstacle limiting the use of CYA as an immunosuppressive agent for renal transplantation. On the other hand, the newly described atrial natriuretic peptide (ANP) hormonal system in both humans and animals appears to play an important role in sodium and water excretion. The present study examined the nephrotoxicity of CYA and the effect of recombinant-ANP (r-ANP) on the damaged kidneys in three groups. Group 1 consisted of rats with 45 minutes warm ischemic left kidney and right nephrectomy [WI rats]; Group 2 consisted of WI rats with oral administration of CYA (100mg/kg/day) for 2 weeks [WI+CYA rats]; Group 3 consisted of WI+CYA rats with intraperitoneal administration of r-ANP (10ng/kg/day) for 2 weeks. Group 2 had lower glomerular filtration rates (GFR) and renal plasma flow (RPF) than Group 1, but Group 3 had significantly higher GFR and RPF than Group 2. Additionally, in order to demonstrate the change in renal viability among the three groups, the adenosine triphosphoric acid level (ATP) and adenylate energy charge ratio (EC) of renal parenchymal tissue were measured by high performance liquid chromatography (HPLC). Group 2 had lower ATP and EC than Group 1, and Group 3 had higher ATP and EC than Group 2. The results of this study suggest that r-ANP is efficacious on rat kidney damage induced by CYA and WIT.
Yoshida
K
K
Department of Urology, Nara Medical University, Japan.
Kagebayashi
Y
Y
Saka
T
T
Yoneda
T
T
Tani
M
M
Ota
M
M
Okajima
E
E
Ozono
S
S
Hirao
Y
Y
Okajima
E
E
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D016572:Cyclosporine / Q000633:toxicity*; D007511:Ischemia / Q000517:prevention & control*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology
D011994:Recombinant Proteins; D016572:Cyclosporine; D009320:Atrial Natriuretic Factor