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Potential uremic toxins modulate energy metabolism of cardiac myocytes in vitro.
- Source :
-
Experimental nephrology [Exp Nephrol] 1997 May-Jun; Vol. 5 (3), pp. 194-200. - Publication Year :
- 1997
-
Abstract
- In the present study we investigated the direct effects of potential uremic toxins on the energy metabolism of cultured cardiac myocytes. High-energy phosphates were extracted with perchloric acid and determined by high performance liquid chromatography. Energy charge (calculated from the ratio of [ATP], [ADP] and [AMP] was significantly reduced by 20 mM urea and the combination of creatinine (5 mM) plus urea (200 mM). On the other hand, perfusion with culture media containing clinically relevant amounts of urea (20 mM) or creatinine (1 mM) increased the PCr/ATP ratio. This effect was more pronounced after application of an artificial uremic medium (consisting of uremic serum, urea, creatinine and cytokines) or high amounts of creatinine (5 mM) plus urea (200 mM). As contractility of myocytes is reduced due to application of uremic compounds or uremic serum, we attribute changes in contraction frequency or inotropy to dysregulation of calcium availability within the cell. In fact, the cardiodepressive action of uremic serum (2.5%) could be completely reversed by the calcium agonist, Bay K 8644, thus indicating disturbances in myocardial calcium homeostasis in uremia. Altered calcium regulation by uremic toxins might therefore be responsible for the observed changes in myocardial energy metabolism. These results might contribute to the understanding of the pathogenesis of cardiac damage in end-stage renal disease.
- Subjects :
- Adenine Nucleotides metabolism
Animals
Cardiomyopathies etiology
Cardiomyopathies metabolism
Cardiomyopathies physiopathology
Cells, Cultured
Creatinine metabolism
Creatinine toxicity
Heart drug effects
Heart physiopathology
In Vitro Techniques
Mice
Myocardial Contraction drug effects
Myocardium cytology
Urea metabolism
Urea toxicity
Uremia complications
Uremia physiopathology
Energy Metabolism drug effects
Myocardium metabolism
Uremia metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1018-7782
- Volume :
- 5
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Experimental nephrology
- Publication Type :
- Academic Journal
- Accession number :
- 9208278