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Research ArticleArticle

Metabolic Effects of Epinephrine in the Perfused Rat Heart

I. Comparison of Intracellular Redox States, Tissue pO2, and Force of Contraction

JOHN R. WILLIAMSON and D. JAMIESON
Molecular Pharmacology June 1966, 2 (3) 191-205;
JOHN R. WILLIAMSON
Johnson Research Foundation, University of Pennsylvania, Philadelphia, Pennsylvania
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D. JAMIESON
Johnson Research Foundation, University of Pennsylvania, Philadelphia, Pennsylvania
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Abstract

A direct fluorometric technique for recording the intracellular oxidation-reduction state has been applied to the perfused rat heart. The fluorescence changes were calibrated in terms of the content of analytically determined NADH and NADPH. Simultaneous measurements of the contractile force and tissue oxygen tension were also made.

The kinetics of the fluorescence response to epinephrine were determined under a variety of conditions which allowed an initial oxidation of pyridine nucleotide to be distinguished from the subsequent predominant increase of reduced pyridine nucleotide. The change of the pyridine nucleotide toward the more oxidized state coincided with increased respiratory activity and an increased force of contraction. This effect is interpreted as a mitochondrial response to the increased ADP formed by the increased work of the heart. The increased formation of reduced pyridine nucleotides was transient, and completely inhibited by iodoacetate. This response is interpreted as being due to the rapid formation of NADH at the glyceraldehyde-P dehydrogenase step as glycogenolysis is initiated.

Log dose-response curves for the contractile force and increase of fluorescence are reported together with data showing inhibition of both these effects by the β-receptor blocking agent, Nethalide. A comparison of the tissue oxygen tension changes in hearts subjected to anoxia and epinephrine suggests that respiratory linked reduction of pyridine nucleotide does not occur during the cycle of pyridine nucleotide reduction following epinephrine administration. The results demonstrate a temporal separation between the positive inotropic action of epinephrine and its glycogenolytic effect.

ACKNOWLEDGMENT This work was supported by the U. S. Public Health Service grant No. 12202-01. J. R. W. is the recipient of a Wellcome Foundation travel grant D. J. is the recipient of a travel grant from the Anti-Cancer Council of Victoria, and the Cancer Institute Board, Victoria, Australia.

  • Copyright ©, 1966, by Academic Press Inc.

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Molecular Pharmacology
Vol. 2, Issue 3
1 Jun 1966
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Research ArticleArticle

Metabolic Effects of Epinephrine in the Perfused Rat Heart

JOHN R. WILLIAMSON and D. JAMIESON
Molecular Pharmacology June 1, 1966, 2 (3) 191-205;

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Research ArticleArticle

Metabolic Effects of Epinephrine in the Perfused Rat Heart

JOHN R. WILLIAMSON and D. JAMIESON
Molecular Pharmacology June 1, 1966, 2 (3) 191-205;
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