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The effect of renal administration of a selective cyclooxygenase-2 inhibitor or stable prostaglandin I2 analog on the progression of sclerotic glomerulonephritis in rats
Background and methods There is increasing evidence that a change in glomerular hemodynamics may promote the development of glomerulosclerosis. In this study, we focused on the pharmacological effects of 2 contrasting agents, etodolac, a preferential cyclooxygenase-2 inhibitor, and beraprost sodium...
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Published in: | Clinical and experimental nephrology 2012-04, Vol.16 (2), p.221-230 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Background and methods
There is increasing evidence that a change in glomerular hemodynamics may promote the development of glomerulosclerosis. In this study, we focused on the pharmacological effects of 2 contrasting agents, etodolac, a preferential cyclooxygenase-2 inhibitor, and beraprost sodium (BPS), a prostaglandin I
2
analog, delivered renally, on the disease course of progressive anti-Thy-1 (ATS) glomerulonephritis.
Results
Intravital microscopic analysis showed that the diameters of glomerular capillaries and glomerular blood flow in unilaterally nephrectomized (Nx) rats treated locally with BPS were significantly increased, as compared to those of Nx rats treated locally with normal saline (NS) or etodolac. We then examined the effects of BPS and etodolac on the course of progressive glomerulosclerosis. Mesangial cell proliferation, adhesion of glomerular capillary tufts and crescent formation in the BPS-treated group appeared to be more severe compared to the ATS + NS and the ATS + etodolac groups. Scoring of mesangial proliferation and glomerulosclerosis revealed that local BPS treatment significantly worsened glomerular pathology. At day 28, there were significant differences in blood flow between the ATS + etodolac group and both the ATS + NS and ATS + BPS groups, indicating that local treatment with etodolac enhanced the recovery of glomerular circulation.
Conclusion
This study provides hemodynamic-based evidence showing that disturbance of intraglomerular microcirculation is a critical marker for progressive glomerulonephritis. |
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ISSN: | 1342-1751 1437-7799 |
DOI: | 10.1007/s10157-011-0558-2 |