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Nitric oxide synthesis and nitric oxide synthase expression in the kidney of rats treated by FK506
Author(s) -
WANG LiMing,
KUBODERA Satoshi,
ARAKI Isao,
UENO Akira,
TAKEDA Masayuki
Publication year - 2002
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1046/j.1440-1797.2002.00073.x
Subject(s) - nephrotoxicity , nitric oxide synthase , endocrinology , medicine , enos , kidney , renal cortex , endothelial nos , creatinine , nitric oxide , renal function , blood urea nitrogen
SUMMARY: FK506‐induced nephrotoxicity is characterized by a disturbance in renal haemody‐namics that is attributed to an imbalance between the various modulators of renal vascular tone. It has not been well defined whether nitric oxide (NO), as an important vasoactive factor, is involved in FK506‐induced nephrotoxicity. This study was designed to evaluate the involvement of nitric oxide in FK506‐induced nephrotoxicity by investigating NO synthesis and NO synthase (NOS) expression in the kidney of rats treated with FK506. Male Wistar rats weighing 240–260 g, aged 11 weeks, were administered with FK506 (3.2mg/kg per day i.m.) for 4 weeks. Renal function and urinary NOx was measured using biochemical methods at the end of both 2 and 4 weeks of treatment. Expression of NOS protein and NOS mRNA in the kidney was also investigated using Western blot analysis and reverse transcription/polymerase chain reaction, respectively. FK506 administration induced nephrotoxicity, which was indicated by renal dysfunction (elevated blood urea nitrogen and creatinine, and reduced creatinine clearance, P < 0.05 vs control). FK506‐induced nephrotoxicity was accompanied by higher urinary NOx excretion at the end of 2 weeks' treatment. In parallel with an increase in NO synthesis, increased eNOS protein and mRNA expression were also found in the renal medulla and renal cortex at week 2. the expression remained at higher levels in the renal medulla and returned to normal levels in the renal cortex at week 4. FK506 treatment induced nephrotoxicity in rats, which was accompanied by a temporal increase in NO synthesis in the kidney. Increased eNOS protein and mRNA expression were also found in the kidney of treated rats, which may be responsible for the enhanced NO synthesis.