title: beta-Agonist stimulation produces changes in cardiac AMPK and coronary lumen LPL only during increased workload.
abstract: Given the importance of lipoprotein lipase (LPL) in cardiac and vascular pathology, the objective of the present study was to investigate whether the beta-agonist isoproterenol (Iso) influences cardiac LPL. Incubation of quiescent cardiomyocytes with Iso for 60 min had no effect on basal, intracellular, or heparin-releasable (HR)-LPL activity. Similarly, Iso did not change HR-LPL in Langendorff isolated hearts that do not beat against an afterload. In the intact animal, LPL activity at the vascular lumen increased significantly in the Iso-treated group, together with a substantial increase in rate-pressure product. This LPL increase was likely via mechanisms regulated by activation of AMP-activated protein kinase (AMPK) and inactivation of acetyl-CoA carboxylase (ACC280). In glucose-perfused hearts, simply switching from Langendorff to the isolated working heart (that beats against an afterload) induced increases in AMPK and ACC280 phosphorylation and enhanced HR-LPL activity. Provision of insulin and albumin-bound palmitic acid to the working heart was able to reverse these effects. In these hearts, introduction of Iso to the buffer perfusate duplicated the effects seen when this beta-agonist was given in vivo. Our data suggest that Iso can influence HR-LPL only during conditions of increased workload, mechanical performance and excessive energy expenditure, and likely in an AMPK-dependent manner.
authors.affiliation: Faculty of Pharmaceutical Sciences, The Univ. of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Ding
authors.initials: D
authors.lastname: An
authors.forename: Girsh
authors.initials: G
authors.lastname: Kewalramani
authors.forename: Dake
authors.initials: D
authors.lastname: Qi
authors.forename: Thomas
authors.initials: T
authors.lastname: Pulinilkunnil
authors.forename: Sanjoy
authors.initials: S
authors.lastname: Ghosh
authors.forename: Ashraf
authors.initials: A
authors.lastname: Abrahani
authors.forename: Rich
authors.initials: R
authors.lastname: Wambolt
authors.forename: Michael
authors.initials: M
authors.lastname: Allard
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Innis
authors.forename: Brian
authors.initials: B
authors.lastname: Rodrigues
mesh_terms: D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000201:enzymology; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical
chemical_list: D000318:Adrenergic beta-Agonists; D009097:Multienzyme Complexes; D012313:RNA; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D008071:Lipoprotein Lipase; D000103:Acetyl-CoA Carboxylase; D007545:Isoproterenol