Post-transplant hypertension in the rat: effects of captopril and native nephrectomy.
In patients with well-functioning renal allografts, the presence of diseased native kidneys appears to be a common cause of elevated blood pressure. We evaluated the role of native kidneys in post-transplant hypertension using a rat model in which the confounding variables of rejection and immunosuppression could be eliminated. To produce disease in native kidneys. PVG rats were subjected to 5/6 nephrectomy. Four weeks following renal ablation, these hypertensive animals were transplanted with kidneys from syngeneic PVG donors. Four weeks later, the effects of captopril and native nephrectomy on blood pressure and renal hemodynamics were examined. Animals with remnant native kidneys which received non-rejecting renal isografts had sustained hypertension, elevated plasma renin levels and reduced transplant function. In these animals, administration of captopril reduced systemic blood pressure. Despite the reduction in blood pressure, PAH clearance by the transplanted kidney increased markedly while GFR rose modestly. Removal of the remnant native kidney also acutely lowered blood pressure. However, compared to captopril, native nephrectomy produced a more marked increase in GFR without significantly affecting renal blood flow. In this model of post-transplant hypertension in the rat, elevated blood pressure and reduced isograft function are mediated by the diseased native kidney, in part through the effects of angiotensin II. These data suggest that ACE inhibitors and native nephrectomy may have beneficial hemodynamic effects in patients with post-transplant hypertension caused by native kidneys.
Coffman
T M
TM
Department of Medicine, Duke University, Medical Center, Durham, North Carolina.
Himmelstein
S
S
Best
C
C
Klotman
P E
PE
D000618:Aminohippuric Acids / Q000493:pharmacokinetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006977:Hypertension, Renal / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D007444:Inulin / Q000493:pharmacokinetics; D007668:Kidney / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood
D000618:Aminohippuric Acids; D007444:Inulin; D002216:Captopril; D012083:Renin