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01.04.2008 | Original Article

Blockade of serotonin 2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy

verfasst von: Shinya Kobayashi, Minoru Satoh, Tamehachi Namikoshi, Yoshisuke Haruna, Sohachi Fujimoto, Sayaka Arakawa, Norio Komai, Naruya Tomita, Tamaki Sasaki, Naoki Kashihara

Erschienen in: Clinical and Experimental Nephrology | Ausgabe 2/2008

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Abstract

Background

Serotonin (5-HT) is involved in vascular inflammation and atherosclerogenesis. Serum 5-HT concentrations are elevated in diabetes, and 5-HT is involved in diabetic vasculopathies. Sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, has renoprotective effects, but its effect in diabetic nephropathy is not elucidated. The aim of this study was to examine the effects of sarpogrelate on endothelial dysfunction in rats with streptozotocin (STZ)-induced diabetes.

Methods

Rats with STZ-induced diabetes were either untreated or treated with sarpogrelate (30 mg/kg P.O.) for 8 weeks. At the end of the experiment, we measured urinary albumin excretion, serum adiponectin concentration and platelet-derived microparticles. Intraglomerular coagulation was detected by immunostaining for platelets. Production of renal reactive oxygen species (ROS) and nitric oxide (NO) was investigated by confocal laser microscopy and used as an index of glomerular endothelial dysfunction.

Results

Diabetic nephropathy was associated with enhanced production of ROS and diminished bioavailable NO in the glomeruli. Treatment with sarpogrelate improved ROS/NO imbalance in glomeruli, suppressed platelet aggregation in glomeruli, reduced platelet-derived microparticles, increased serum adiponectin level and reduced the level of albuminuria, compared with non-treated diabetic rats.

Conclusions

Our results indicate that sarpogrelate improves endothelial function in rats with STZ-induced diabetes through a reduction of glomerular platelet activation and an increase in serum adiponectin concentrations and suggest that sarpogrelate is potentially useful for the treatment of diabetic nephropathy.

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Titel: Blockade of serotonin 2A receptor improves glomerular endothelial function in rats with streptozotocin-induced diabetic nephropathy
verfasst von: Shinya Kobayashi
Minoru Satoh
Tamehachi Namikoshi
Yoshisuke Haruna
Sohachi Fujimoto
Sayaka Arakawa
Norio Komai
Naruya Tomita
Tamaki Sasaki
Naoki Kashihara
Publikationsdatum: 01.04.2008
Verlag: Springer Japan
Erschienen in: Clinical and Experimental Nephrology / Ausgabe 2/2008
Print ISSN: 1342-1751
Elektronische ISSN: 1437-7799
DOI: https://doi.org/10.1007/s10157-007-0011-8

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Abstract

Background

Methods

Results

Conclusions

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