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-dependent factors are of greater important.
Szabo
A
A
Department of Nephrology, University Hospital Essen, Germany.
Patschan
O
O
Kuttler
B
B
Müller
V
V
Philipp
T
T
Rettig
R
R
Heemann
U
U
D000818:Animals; D002908:Chronic Disease; D018450:Disease Progression; D006084:Graft Rejection / Q000209:etiology*; D006973:Hypertension / Q000150:complications*; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors