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Adenosine A 2 a receptor stimulation prevents proteinuria in diabetic rats by promoting an anti‐inflammatory phenotype without affecting oxidative stress
Author(s) -
Persson P.,
FriederichPersson M.,
Fasching A.,
Hansell P.,
Inagi R.,
Palm F.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12511
Subject(s) - medicine , endocrinology , diabetes mellitus , kidney , oxidative stress , streptozotocin , renal function , inflammation , adenosine receptor , diabetic nephropathy , adenosine , stimulation , agonist , receptor
Aim Diabetic patients are at increased risk for kidney disease. There is presently no clinical treatment available that effectively protects kidney function in diabetics. This study investigates whether chronic stimulation of the adenosine A 2a receptor (A 2a AR ) protects kidney function in insulinopenic diabetic rats. Methods Streptozotocin‐induced diabetic rats and corresponding controls were chronically treated with the adenosine A 2a AR agonist CGS 21680 throughout the four‐week diabetes duration. Kidney function was thereafter investigated, and urine and plasma samples were collected for analysis of protein, oxidative stress and inflammatory markers. Results Glomerular filtration rate, renal blood flow, filtration fraction and diabetes‐induced kidney hypoxia were all unaffected by chronic A 2a AR stimulation. Furthermore, diabetic rats had increased oxidative stress, which was further increased by chronic A 2a AR stimulation. However, the 10‐fold increased urinary protein excretion observed in the diabetic rats was completely prevented by chronic A 2a AR stimulation. These beneficial effects were accompanied by reduced levels of the pro‐inflammatory TNF ‐ α and increased levels of the anti‐inflammatory IL ‐10 as well as decreased infiltration of macrophages, glomerular damage and basement membrane thickness. Conclusion Chronic A 2a AR stimulation prevents proteinuria and glomerular damage in experimental diabetes via an anti‐inflammatory mechanism independent of oxidative stress and kidney hypoxia.