Hypertension accelerates the pace of chronic graft dysfunction in the rat

In this study we compared the effects of hypertension on chronic rejection in a rat model of renal transplantation utilizing genetically normotensive (BBOK) and spontaneously hypertensive rats (SHR). SHR received either a BBOK (BBOK → SHR) or an SHR (SHR → SHR) kidney; normotensive isografts served as controls. Before transplantation, SHR recipients were treated with hydralazine (50 mg/kg per day). To prevent acute rejection, an anti-CD4 antibody (3 mg/kg per day for 3 weeks) in combination with cyclosporin A (3 mg/kg per day for 1 week) was given to all groups. Six weeks after transplantation, blood pressure was measured, and the kidneys removed for histological and immunohistological analysis. SHR → SHR developed a significantly higher blood pressure than BBOK → SHR. Blood pressure in BBOK → BBOK was significantly lower than in the other two groups. The degree of glomerulosclerosis was similarly increased in allografted (BBOK → SHR) and SHR → SHR kidneys as compared with the BBOK → BBOK kidneys (P < 0.05). Infiltration of ED-1⁺ monocyte/macrophages and OX19 pan-T-cells was most pronounced in allografts (BBOK → SHR) and was also increased in SHR → SHR as compared with BBOK → BBOK. Our results indicate that hypertension accelerates the morphological and immunohistological changes characteristic of grafts undergoing chronic rejection. However, our findings support the hypothesis that alloantigen-dependentfactors are of greater important.