Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart.
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 muCi/kg of either [1-(14)C]palmitic acid ([1-(14)C]16:0) or [1-(14)C]arachidonic acid ([1-(14)C]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 lambda was increased in [1-(14)C]20:4 n-6-infused rats, which indicates that less 20:4 n-6 was recycled in denervated rats. In [1-(14)C]16:0-infused rats, incorporation rate and turnover values of 16:0 in stable lipid compartments were unchanged, which is indicative of preservation of beta-oxidation. In [1-(14)C]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 A(2) 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 A(2) activity.
Patrick
Casey B
CB
Dept. of Pharmacology, Physiology, and Therapeutics, School of Medicine and Health Sciences, Univ. of North Dakota, 501 N. Columbia Rd., Rm. 3700, Grand Forks, ND 58202-9037, USA.
McHowat
Jane
J
Rosenberger
Thad A
TA
Rapoport
Stanley I
SI
Murphy
Eric J
EJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003714:Denervation; D006329:Heart Conduction System / Q000187:drug effects; D008297:Male; D016627:Oxidopamine; D011865:Radioisotope Dilution Technique; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D002250:Carbon Radioisotopes; D016718:Arachidonic Acid; D016627:Oxidopamine