Renal responses to atrial natriuretic peptide (ANP) in rats with non-oliguric acute renal failure induced by cisplatin.
This study was designed to compare the renal effects of atrial (A-type) natriuretic peptide (ANP) on control (saline-injected) rats and rats with non-oliguric acute renal failure induced by cisplatin. The results obtained here are summarized as follows: (1) In the metabolic cage study, cisplatin-treated rats showed increases in blood urea nitrogen and serum creatinine while creatinine clearance decreased to the lowest levels on day 4. A transient increase in urinary protein was observed at day 4. (2) ANP infusion significantly increased urine flow rate (UFR), creatinine clearance (CCr), fractional excretion rates of sodium (FENa) and chloride (FECl), and urinary phosphorus and magnesium (Mg) excretions in a dose-dependent manner without affecting renal plasma flow and fractional excretion rates of potassium and urea in cisplatin-treated rats. (3) Renal effects of ANP on UFR, CCr, FENa, FECl and excretion of Mg were more pronounced in cisplatin-treated rats compared to control rats although markedly blunted responses to ANP have been reported in nephrotic patients and nephrotic animals induced by adriamycin and aminonucleoside. (4) Histological examination showed extensive necrosis of the S3 segment of the proximal tubule located in the outer stripe of the outer medulla with minimal glomerular abnormalities in the kidney of cisplatin-treated rats. In conclusion, the main mechanism of the increased renal responses to ANP is considered to be due to an increased delivery of sodium, fluid and ANP itself to the inner medullary collecting duct which is the major renal site of action of ANP under the condition of acute proximal tubular necrosis by cisplatin.
Nagano
N
N
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
Yagi
M
M
Kato
S
S
Furuya
Y
Y
Miyata
S
S
Manabe
N
N
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000503:physiopathology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects / Q000502:physiology; D004573:Electrolytes / Q000652:urine; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007679:Kidney Medulla / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D008297:Male; D011507:Proteinuria; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects; D013997:Time Factors
D004573:Electrolytes; D009320:Atrial Natriuretic Factor; D003404:Creatinine; D002945:Cisplatin