ANTIHYPERTENSIVE DRUG-TREATMENT IN CHRONIC RENAL-ALLOGRAFT REJECTION IN THE RAT - EFFECT ON STRUCTURE AND FUNCTION

To gain insight into the contribution of immunologic and hemodynamic f actors 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 hyd rostatic pressures of rat renal allografts with chronic rejection. Rec ipient 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 hyd rochlorothiazide, the angiotensin-converting enzyme inhibitor cilazapr il, or the angiotensin II receptor blocker L-158,809. Grafts in untrea ted recipients developed chronic interstitial inflammation, as well as vascular and glomerular lesions consistent with chronic rejection. Th ese lesions were associated with immunohistochemical loss of the negat ively charged heparan sulfate proteoglycan side chain. All treatment r egimens 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 histo logical manifestations of rejection, and antihypertensive drugs decrea sed the extent of glomerular mesangiolysis and glomerulosclerosis; L-1 58,809 and cilazapril also inhibited graft atherosclerosis and tubular atrophy. We conclude that chronic rejection is primarily an immune-me diated process, but hemodynamic and angiotensin II-mediated effects ma y play a pivotal role in the expression of immune-mediated lesions.