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Am J Physiol Endocrinol Metab 288: E1120-E1127, 2005. First published February 1, 2005; doi:10.1152/ajpendo.00588.2004
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{beta}-Agonist stimulation produces changes in cardiac AMPK and coronary lumen LPL only during increased workload

Ding An,1 Girsh Kewalramani,1 Dake Qi,1 Thomas Pulinilkunnil,1 Sanjoy Ghosh,1 Ashraf Abrahani,1 Rich Wambolt,2 Michael Allard,2 Sheila M. Innis,3 and Brian Rodrigues1

1Faculty of Pharmaceutical Sciences, Departments of 2Pathology and Laboratory Medicine and 3Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada

Submitted 13 December 2004 ; accepted in final form 27 January 2005

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.

isoproterenol; acetyl-coenzyme A carboxylase; cardiomyocyte; Langendorff heart; working heart; adenosine 3',5'-monophosphate-activated protein kinase; lipoprotein lipase


Address for reprint requests and other correspondence: B. Rodrigues, Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The Univ. of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3 (E-mail: rodrigue{at}interchange.ubc.ca)




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