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Sympathoadrenergic overactivity and lipid metabolism

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Summary

Epidemiological studies have identified high heart rates as a risk factor for coronary heart disease mortality, and heart rate was found to correlate with the severity of coronary atherosclerosis. Heart rate was positively correlated with serum concentrations of total cholesterol, triglycerides, and non-HDL cholesterol. Since heart rate responds sensitively to sympathoadrenergic activity, it was hypothesized that catecholamines play a crucial role in the unfavorable lipid alterations. In addition to influences on circulating lipids, the question arose whether catecholamines have more specific effects on molecular species of structural lipids. Of particular importance is the question of the involvement of catecholamines in the recently suggested correlation between arachidonic acid and stroke mortality. It is therefore attempted to delineate the possible effects of catecholamines on the fatty acid composition of the phospholipids of heart muscle and vasculature. This was achieved in rats by either catecholamine injection or by swimming, a condition known to be associated with marked sympatho-adrenergic stimulation. In swimming rats, linoleic acid was decreased by up to 40% in heart phospholipids, whereas stearic acid and arachidonic acid were increased. Similarly, chronic norepinephrine treatment in rats resulted in a net decrease in linoleic acid and an increase in arachidonic acid and docosahexaenoic acid, which was particularly pronounced when rats were fed an n-3 polyunsaturated fatty acid (PUFA)-rich oil diet. Thus, catecholamines do affect the PUFA composition of heart membranes, mainly through an increase in arachidonic acid content. To further define the action of catecholamines on structural lipids, isolated rat ventricular myocytes in culture were subjected four times to 30 minutes of isoproterenol (10-6 M) stimulation over 48 hours. No changes in membrane lipid parameters were observed, although the beating rate was increased by 30% during the stimulation. When the cell membranes were enriched in n-3 PUFAs (in association with a decrease in arachidonic acid), the positive chronotropic effect elicited by isoproterenol was raised to +50%, indicating the modulation of adrenergic function by membrane PUFAs. However, isoproterenol treatment again had no effect on the phospholipid fatty acid composition. Thus, the effect of catecholamines on membrane lipids observed in intact organism appears to be indirect and to involve most probably organs such as the liver and adipose tissue. Catecholamines are expected to induce a lipolysis-linked quantitative and qualitative alteration in circulating fatty acids, which in turn alter the heart membrane composition, similar to the composition changes elicited by diet lipid alterations. Since there is increasing evidence that such fatty acid changes affect the activity of membrane proteins, the possibility emerges that this mechanism may contribute to the catecholamine-linked cardiovascular mortality.

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Authors and Affiliations

  1. Unité de Nutrition Lipidique, INRA, Dijon, France

    Alain Grynberg

  2. Solvay Pharma, Hannover, Germany

    Dieter Ziegler

  3. Molecular Cardiology Laboratory, Centre of Internal Medicine, University of Marburg, Germany

    Heinz Rupp

Authors
  1. Alain Grynberg
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  2. Dieter Ziegler
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  3. Heinz Rupp
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Grynberg, A., Ziegler, D. & Rupp, H. Sympathoadrenergic overactivity and lipid metabolism. Cardiovasc Drug Ther 10 (Suppl 1), 223–230 (1996). https://doi.org/10.1007/BF00120491

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  • DOI: https://doi.org/10.1007/BF00120491

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