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.
Many renal transplants undergo gradual deterioration in structure and function in the months or years after transplantation. The processes that underlie this progressive decline have not been defined, and may include immunological and nonimmunological mechanisms. The present experiments were designed to investigate the glomerular capillary hydrostatic pressure in long-surviving rat renal transplants with or without chronic rejection. Stop-flow glomerular pressures were measured in F344 renal allografts with chronic rejection, syngeneic F344 grafts, and long-surviving syngeneic and allogeneic LEW grafts without chronic rejection; control measurements were done in nontransplanted intact animals or after subtotal renal ablation. Renal ablation or transplantation resulted in increased glomerular pressure in F344 but not LEW kidneys; the glomerular pressure in syngeneic F344 grafts was not different from that in allogeneic F344 grafts. There was no correlation between the mean arterial pressure and the glomerular capillary pressure. Our data suggest that the glomerular capillary pressure is determined by local intrarenal factors. The glomerular capillary pressure in allotransplanted kidneys resembles that of the donor kidney after subtotal renal ablation. The importance of increased glomerular pressure in the progressive decline of graft function of chronic rejection remains to be established.
Journal Article Spontaneous diastolic contractions and phosphorylation of the cardiac ryanodine receptor at serine-2808 in congestive heart failure in rat Get access Masakazu Obayashi, Masakazu Obayashi aDepartment of Medical Bio-regulation, Division of Cardiovascular Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Bailong Xiao, Bailong Xiao bDepartments of Medicine, Physiology and Biophysics, Health Sciences Center, University of Calgary, Calgary, Alberta, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Bruno D. Stuyvers, Bruno D. Stuyvers bDepartments of Medicine, Physiology and Biophysics, Health Sciences Center, University of Calgary, Calgary, Alberta, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Allen W. Davidoff, Allen W. Davidoff bDepartments of Medicine, Physiology and Biophysics, Health Sciences Center, University of Calgary, Calgary, Alberta, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Jie Mei, Jie Mei bDepartments of Medicine, Physiology and Biophysics, Health Sciences Center, University of Calgary, Calgary, Alberta, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar S.R. Wayne Chen, S.R. Wayne Chen bDepartments of Medicine, Physiology and Biophysics, Health Sciences Center, University of Calgary, Calgary, Alberta, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Henk E.D.J. ter Keurs Henk E.D.J. ter Keurs * bDepartments of Medicine, Physiology and Biophysics, Health Sciences Center, University of Calgary, Calgary, Alberta, Canada *Corresponding author. Department of Physiology/Biophysics, University of Calgary, 3330 Hospital Drive, NW, Calgary, Alberta, Canada, T2N 4N1. Tel.: +1 403 289 7156; fax: +1 403 270 0313. Email address: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 69, Issue 1, January 2006, Pages 140–151, https://doi.org/10.1016/j.cardiores.2005.07.010 Published: 01 January 2006 Article history Received: 18 February 2005 Revision received: 07 July 2005 Accepted: 11 July 2005 Published: 01 January 2006
