Antihypertensive drug treatment in chronic renal allograft rejection in the rat - Effect on structure and function

被引:78
|
作者
Benediktsson, H
Chea, R
Davidoff, A
Paul, LC
机构
[1] UNIV CALGARY,DEPT PATHOL,CALGARY,AB,CANADA
[2] UNIV TORONTO,ST MICHAELS HOSP,DEPT MED,TORONTO,ON M5B 1W8,CANADA
[3] TORONTO HOSP,TORONTO,ON M5T 2S8,CANADA
关键词
D O I
10.1097/00007890-199612150-00018
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To gain insight into the contribution of immunologic and hemodynamic factors in the progressive demise of structure and function in chronic renal allograft dysfunction, we studied the histological changes, the immunostainable glomerular anionic sites, and glomerular capillary hydrostatic pressures of rat renal allografts with chronic rejection. Recipient animals were left untreated, received 8 weeks of treatment with the immunosuppressive drug cyclosporine, or received antihypertensive drugs consisting of the combination of reserpine, hydralazine and hydrochlorothiazide, the angiotensin-converting enzyme inhibitor cilazapril, or the angiotensin II receptor blocker L-158,809. Grafts in untreated recipients developed chronic interstitial inflammation, as well as vascular and glomerular lesions consistent with chronic rejection. These lesions were associated with immunohistochemical loss of the negatively charged heparan sulfate proteoglycan side chain. All treatment regimens decreased the systemic and glomerular capillary pressures and were associated with no loss of function, decreased proteinuria, and a tendency to improved graft function. Cyclosporine prevented all histological manifestations of rejection, and antihypertensive drugs decreased the extent of glomerular mesangiolysis and glomerulosclerosis; L-158,809 and cilazapril also inhibited graft atherosclerosis and tubular atrophy. We conclude that chronic rejection is primarily an immune-mediated process, but hemodynamic and angiotensin II-mediated effects may play a pivotal role in the expression of immune-mediated lesions.
引用
收藏
页码:1634 / 1642
页数:9
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