Gene expression of intrarenal renin-angiotensin system in streptozotocin-induced diabetic rats

ABSTRACT

In humans and many animal models with chronic progressive renal diseases, angiotensin-converting enzyme (ACE) inhibitor markedly attenuates the progression of nephropathy. Several studies have reported augmented gene expression and redistribution of renal renin in partial nephrectomized rats. Although precise mechanism(s) is not known, the renin-angiotensin system (RAS) may play an important role in the progression of renal diseases. Thus, this study was undertaken to examine the gene expression of renal renin, angiotensinogen, and AT-1 subtypes (AT-1A and AT-1B) in rats with diabetic nephropathy, and the influences of lipopolysaccharide (LPS)-induced septicemia on the gene expression. Four weeks after streptozotocin (STZ) treatment (55 mg/kg, i.p.), rats were randomly divided into LPS-treated (1.6 mg/kg, i.p.) and control rats. At 6 hours after LPS treatment, the rats were killed and the kidney was removed from each rat. Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) techniques were used to detect mRNA expression. STZ treatment markedly attenuated body weight gain and significantly increased blood glucose level. Renal renin content (RRC) was significantly decreased in the STZ-treated rats compared to that in control rats. The renal ACE activity between STZ-treated and control rats was not significantly different. Renal renin mRNA level was prominently increased, while angiotensinogen and AT-1A mRNA levels were slightly decreased in STZ-treated rats compared to those in controls. AT-1B mRNA level did not differ in both groups. Acute LPS treatment did not show any significant changes of mRNA levels of intrarenal RAS components in both groups. These results suggest that intrarenal RAS components were differentially regulated in STZ-treated diabetic rats. Further studies are required to evaluate the relationship between intrarenal RAS and other vasomodulatory systems.