Endothelial function predicts the development of renal damage after combined nephrectomy and myocardial infarction.
It was demonstrated that individual renal endothelial dilatory function of the healthy rat predicts susceptibility to subsequent renal damage induced by 5/6 nephrectomy. In addition, it is reported that myocardial infarction (MI) that was performed upon unilateral nephrectomy (UNx) induced highly variable renal damage. Therefore, whether the variability in renal damage after MI could be explained by the variation in individual renal endothelial function before the induction of injury was studied. Endothelium-dependent relaxation to acetylcholine was investigated in vitro in small arteries that were isolated from the extirpated kidney at UNx. MI was induced 1 wk after UNx by ligation of the left coronary artery. Proteinuria and systolic BP were evaluated weekly for 16 wk thereafter using metabolic cages and the tail-cuff method, respectively. Upon termination of the study, focal glomerulosclerosis was evaluated by histology as an additional marker of renal damage. After MI, nephrectomized male Wistar rats (n = 15) gradually developed variable proteinuria, ranging from 20 to 507 mg/24 h at week 16, with an average systolic BP of 131 +/- 7 mmHg. The individual renal endothelial function of the healthy rats predicted the extent of renal damage in terms of proteinuria (r = -0.62, P = 0.008) and focal glomerulosclerosis (r = -0.70, P = 0.003). The individual level of renal endothelial function in the healthy rat is able to predict the severity of renal damage that is induced by MI. Further exploration of the underlying mechanisms may lead to discovery of preventive renoprotective therapies.
Ochodnický
Peter
P
Department of Clinical Pharmacology, University Medical Centre Groningen, The Netherlands. p.ochodnicky@med.umcg.nl
de Zeeuw
Dick
D
Henning
Robert H
RH
Kluppel
C Alex
CA
van Dokkum
Richard P E
RP
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D001794:Blood Pressure; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology* / Q000502:physiology*; D005923:Glomerulosclerosis, Focal Segmental; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology*; D009392:Nephrectomy; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000109:Acetylcholine