Nagano N, Yagi M, Kato S, Furuya Y, Miyata S, Manabe N
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
J Vet Med Sci. 1995 Dec;57(6):997-1002. doi: 10.1292/jvms.57.997.
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.
本研究旨在比较心房（A型）利钠肽（ANP）对对照组（注射生理盐水）大鼠和由顺铂诱导的非少尿型急性肾衰竭大鼠的肾脏影响。此处获得的结果总结如下：（1）在代谢笼研究中，顺铂处理的大鼠血尿素氮和血清肌酐升高，而肌酐清除率在第4天降至最低水平。在第4天观察到尿蛋白短暂增加。（2）在顺铂处理的大鼠中，ANP输注以剂量依赖方式显著增加尿流率（UFR）、肌酐清除率（CCr）、钠（FENa）和氯（FECl）的分数排泄率以及尿磷和镁（Mg）排泄，而不影响肾血浆流量以及钾和尿素的分数排泄率。（3）与对照大鼠相比，ANP对顺铂处理大鼠的UFR、CCr、FENa、FECl和Mg排泄的肾脏影响更明显，尽管已有报道称阿霉素和氨基核苷诱导的肾病患者和肾病动物对ANP的反应明显减弱。（4）组织学检查显示，顺铂处理大鼠肾脏中外髓质外带近端小管S3段广泛坏死，肾小球异常最小。总之，肾脏对ANP反应增加的主要机制被认为是由于在顺铂导致急性近端小管坏死的情况下，钠、液体和ANP本身向髓质内集合管的输送增加，而髓质内集合管是ANP在肾脏中的主要作用部位。
