期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 287, 期 3, 页码 F384-F392出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00006.2004
关键词
microelectrode; hyperglycemia; confocal imaging; protein kinase C; endothelial nitric oxide synthase
资金
- NHLBI NIH HHS [HL-25824] Funding Source: Medline
- NIDDK NIH HHS [DK-064004, R21 DK064004] Funding Source: Medline
We hypothesized a high concentration of glucose could suppress glomerular endothelial nitric oxide synthase ( eNOS) by a protein kinase C (PKC) mechanism, as has been found in other tissues. Mouse kidney slices ( 150 - 200 mum) were bathed in Hanks' solution with 100 muM L-arginine and exposed to either 5 or 20 - 30 mM D-glucose. Immunofluorescence identified only eNOS in normal mouse glomeruli. Measurements of glomerular NO concentration with NO-sensitive fluorescent dye ( 4,5-diaminofluorescein diacetate) using confocal microscopy and NO-sensitive microelectrodes verified that resting glomeruli had active production of NO that was inhibited by N-G-nitro-L- arginine methyl ester. High-concentration ( 20 - 30 mM) D-glucose inhibited 60 - 70% of the NO production within 15 - 30 min; L-glucose at the same concentration did not have any effect. Inhibition of PKC-beta with 100 nM ruboxistaurin prevented eNOS suppression in high-glucose media. Activation of PKC with 100 nM phorbol ester also suppressed the glomerular NO concentration. We concluded that eNOS in the renal glomerular capillary endothelial cells is suppressed by activity of PKC at high-glucose concentrations comparable to those in diabetic animals and humans. The consequence is a rapid decline in the generation of NO in the glomerular endothelial cells in the presence of a high concentration of glucose.
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