Submitted on June 16, 2004
Accepted on January 18, 2005
Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart
Casey B Patrick1, Jane McHowat2, Thad A Rosenberger1, Stanley I Rapoport1, and Eric J Murphy3*
1 BPMS, NIH, Bethesda, MD, USA
2 Department of Pathology, Saint Louis University, St. Louis, MO, USA
3 BPMS, NIH, Bethesda, MD, USA; Department of Pharmacology, Physiology, and Therapeutics and Department of Chemistry, University of North Dakota, Grand Forks, ND, USA
* To whom correspondence should be addressed. E-mail: emurphy{at}medicine.nodak.edu.
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, i.p.) and infused with either [1-begin super14end superC]palmitic ([1-14C]16:0, 170 µCi/kg) or [1-14C]arachidonic acid ([1-14C]20:4 n-6, 170 µCi/kg) 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 lamda was increased in [1-14C]20:4 n-6 infused rats, which indicates less 20:4 n-6 was recycled in denervated rats. In [1-14C]16:0 infused rats, incorporation rate and turnover of 16:0 in stable lipid compartments was unchanged, indicative of preservation of 
-oxidation. In [1-14C]20:4 n-6 infused rats, there was a dramatic reduction in the incorporation rate (60-84%) and turnover (56-85%) in denervated rats that was dependent upon the lipid compartment. In addition, phospholipase A2 activity was reduced 40% in treated rats, consistent with the reduction observed in 20:4 n-6 turnover. These results demonstrate a marked reduction in 20:4 n-6 incorporation rate and turnover in sympathetic denervated rats, suggesting an effect on lipid-mediated signal transduction mediated by a reduction in PLA2 activity.
