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

Abstract

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 λ 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 β-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 A2activity 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 A2activity.