In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 274, No. 1 ( 1998-01-01), p. H8-H17
Abstract:
Pyruvate has been shown to be a metabolic inotrope in the myocardium. In millimolar concentrations, it has been shown to increase both myocardial phosphorylation potential and the cytosolic [NAD + ]-to-[NADH] ratio. To determine if changes in these parameters can alter intracellular Ca 2+ concentration ([Ca 2+ ] i ) and hence contractile function, Ca 2+ transients and cell shortening (CS) were measured in isolated rat ventricular myocytes superfused with a physiological N-2-hydroxyethylpiperazine- N′-2-ethanesulfonic acid buffer (11 mmol/l glucose) with and without additional pyruvate,l-lactate, acetate, or isoproterenol. The addition of 5 mmol/l pyruvate resulted in a 33% increase in CS and a 39% increase in systolic [Ca 2+ ] i . These pyruvate effects were 70% of those observed with 100 nmol/l isoproterenol. The mitochondrial monocarboxylate transport inhibitor α-cyano-4-hydroxycinnamate (250 μmol/l) strongly inhibited pyruvate inotropy, suggesting a substantial obligatory coupling between pyruvate inotropism and its oxidation by the mitochondria. A possible role of the cytosolic [NAD + ]-to-[NADH] ratio was assessed by comparing the effects of 20 mmol/ll-lactate to those of equimolar pyruvate. In contrast to 20 mmol/l pyruvate, excess l-lactate failed to appreciably increase CS or systolic [Ca 2+ ] i . The findings imply that, at levels substantially above 5 mmol/l, a portion of pyruvate inotropism might be due to extreme cytosolic [NAD + ]-to-[NADH] ratios. This study is the first evidence that augmented [Ca 2+ ] i transients are most likely the mechanism of cardiac pyruvate inotropism.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.1998.274.1.H8
Language:
English
Publisher:
American Physiological Society
Publication Date:
1998
detail.hit.zdb_id:
1477308-9
SSG:
12
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