Journal Article

Capillary/myocyte mismatch in the heart in renal failure—a role for erythropoietin?

Kerstin Amann, Moriz Buzello, Aurelia Simonaviciene, Gabriel Miltenberger‐Miltenyi, Andreas Koch, Alexander Nabokov, Marie‐Luise Gross, Bernhard Gless, Gerhard Mall and Eberhard Ritz

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 15, issue 7, pages 964-969
Published in print July 2000 | ISSN: 0931-0509
Published online July 2000 | e-ISSN: 1460-2385 | DOI: https://dx.doi.org/10.1093/ndt/15.7.964
Capillary/myocyte mismatch in the heart in renal failure—a role for erythropoietin?

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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.

Method. 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/mm3 in controls). It was not statistically different in animals with partial renal ablation+rhEpo+antihypertensive treatment (3620±828 mm/mm3) compared to partial ablation alone.

Conclusion. 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.

Keywords: experimental renal failure; heart; capillarization; rhEpo

Journal Article.  3623 words.  Illustrated.

Subjects: Nephrology

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