title: Capillary/myocyte mismatch in the heart in renal failure--a role for erythropoietin?
abstract: BACKGROUND
  Chronic renal failure is characterized by remodeling of the heart with left ventricular hypertrophy (increasing oxygen demand) and capillary deficit leading to capillary/myocyte mismatch (decreasing oxygen supply). Erythropoietin (Epo) has known angiogenic properties causing endothelial cell activation, migration and sprouting, mediated at least in part via the JAK/STAT (Janus kinase/signal transducers and activators of transcription) pathway. In uraemic cardiac hypertrophy the presence of diminished capillary supply implies that capillary growth does not keep pace with development of hypertrophy. To investigate whether this was due to a deficit of the angiogenic hormone Epo we examined whether Epo levels are altered and whether an increase in haematocrit by administration of rhEpo influences capillary supply, i.e. capillary/myocyte mismatch in experimental renal failure.
  
  
  METHODS
  Male Spraque-Dawley rats were either subjected to partial renal ablation or sham operation. Only modest amounts of renal tissue were removed so that the rats were not anemic. Subgroups of rats received either human (rh)Epo alone or in combination with unspecific antihypertensive treatment (dihydralazine plus furosemide) in order to control the Epo induced rise in blood pressure. Capillary supply was measured stereologically as capillary length per volume myocardium using the orientator method.
  
  
  RESULTS
  Capillary length density was reduced by approximately 25% after partial renal ablation (3237+/-601 vs 4293+/-501 mm/mm(3) in controls). It was not statistically different in animals with partial renal ablation+rhEpo+antihypertensive treatment (3620+/-828 mm/mm(3)) compared to partial ablation alone.
  
  
  CONCLUSIONS
  The study shows that lack of Epo does not cause, or contribute to, the deficit of capillary growth in the hypertrophied left ventricle of rats with renal failure. In addition, a rise in haematocrit is not accompanied by beneficial effects on alterations of cardiovascular structure in experimental renal failure.
authors.affiliation: Department of Pathology, University of Heidelberg, Heidelberg, Germany. kerstin.amann@patho.imed.uni-erlangen.de
authors.forename: K
authors.initials: K
authors.lastname: Amann
authors.forename: M
authors.initials: M
authors.lastname: Buzello
authors.forename: A
authors.initials: A
authors.lastname: Simonaviciene
authors.forename: G
authors.initials: G
authors.lastname: Miltenberger-Miltenyi
authors.forename: A
authors.initials: A
authors.lastname: Koch
authors.forename: A
authors.initials: A
authors.lastname: Nabokov
authors.forename: M L
authors.initials: ML
authors.lastname: Gross
authors.forename: B
authors.initials: B
authors.lastname: Gless
authors.forename: G
authors.initials: G
authors.lastname: Mall
authors.forename: E
authors.initials: E
authors.lastname: Ritz
mesh_terms: D000818:Animals; D002196:Capillaries / Q000473:pathology* / Q000648:ultrastructure; D003326:Coronary Circulation; D004921:Erythropoietin / Q000502:physiology*; D007676:Kidney Failure, Chronic / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004921:Erythropoietin