Abstract:

Objective   To explore changes of the advanced glycosylation end products(AGEs)-receptor of the AGEs(RAGE) system, signal translation system, and related cytokines in the kidneys of spontaneous hypertension rats(SHR), and effects of benazepril on them. Methods   24 SHR were randomly divided into the benazepril (10mg/kg·d) group and the SHR group, and 12 Wistar Kyoto rats(WKY) as the WKY group. An equal amount of distilled water was intragastrically administrated once a day in the SHR and WKY groups. Pulverized benazepril(10mg/kg·d) along with the same amount of distilled water was intragastrically administrated in the benazepril group.12 weeks later, levels of cortex renins AgII and the 24h urine protein were tested and the glomerulosclerosis index(GSI) was calculated. Expressions of AGEs and vascular cell adhesion molecule-1(VCAM-1) in the kidneys were detected by immunofluorescence assay. Expressions of nuclear transcription factor(NF-κB) mRNA and triphosphopyridine nucleotide( NADPH) oxidase p47phox mRNA were measured by RT-PCR. Expression of the NF-κB protein was measured by Western blot. Results   Compared with the WKY group, the levels of Ang II in the kidneys, albuminuria and GSI were significantlyhigher in the SHR group(P<0.01), while they were significantly reduced by benazepril(P<0.01). Compared with the WKY group, expressions of AGEs, VCAM-1, NF-κB and NADPH oxidase p47phox were significantly higher in the SHR group(P<0.01), while they were significantly reduced by benazepril(P<0.01). Conclusion   Oxidation stress in the kidneys is increased in SHR. Combination of AGEs and RAGE can activate NFκB, increased expressions of VCAM and NADPH oxidase p47phox, and accelerate injury to kidneys. By suppressing oxidative stress and expressions of AGEs, benazepril further inhibits expressions of NF-κB and growth factor and eases injury to kidneys induced by hypertension.

Key words: Benazepril; Hypertension; Glycosylation end products, advanced; Rats, spontaneously hypertensive