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This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/H2611    most recent 00549.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Patrick, C. B. Articles by Murphy, E. J. Search for Related Content PubMed PubMed Citation Articles by Patrick, C. B. Articles by Murphy, E. J.

Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart

¹Section on Brain Physiology and Metabolism, National Institute on Aging, National Institutes of Health, Bethesda, Maryland; ²Department of Pathology, Saint Louis University, St. Louis, Missouri; and ³Department of Pharmacology, Physiology, and Therapeutics, and Department of Chemistry, University of North Dakota, Grand Forks, North Dakota

Submitted 16 June 2004 ; accepted in final form 18 January 2005

Heart sympathetic denervation can accompany Parkinson's disease, but the effect of this denervation on cardiac lipid-mediated signaling is unknown. To address this issue, rats were sympathetically denervated with 6-hydroxydopamine (6-OHDA, 50 mg/kg ip) and infused with 170 µCi/kg of either [1-¹⁴C]palmitic acid ([1-¹⁴C]16:0) or [1-¹⁴C]arachidonic acid ([1-¹⁴C]20:4 n-6), and kinetic parameters were assessed using a steady-state radiotracer model. Heart norepinephrine and epinephrine levels were decreased 82 and 85%, respectively, in denervated rats, and this correlated with a 34% reduction in weight gain in treated rats. Fatty acid tracer uptake was not significantly different between groups for either tracer, although the dilution coefficient was increased in [1-¹⁴C]20:4 n-6-infused rats, which indicates that less 20:4 n-6 was recycled in denervated rats. In [1-¹⁴C]16:0-infused rats, incorporation rate and turnover values of 16:0 in stable lipid compartments were unchanged, which is indicative of preservation of -oxidation. In [1-¹⁴C]20:4 n-6-infused rats, there were dramatic reductions in incorporation rate (60–84%) and turnover value (56–85%) in denervated rats that were dependent upon the lipid compartment. In addition, phospholipase A₂ activity was reduced 40% in treated rats, which is consistent with the reduction observed in 20:4 n-6 turnover. These results demonstrate marked reductions in 20:4 n-6 incorporation rate and turnover in sympathetic denervated rats and thereby suggest an effect on lipid-mediated signal transduction mediated by a reduction in phospholipase A₂ activity.

palmitic acid; signal transduction; phospholipase A₂; catecholamines; phospholipids