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-agonist stimulation produces changes in cardiac AMPK and coronary lumen LPL only during increased workload
1 Department of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada
2 Departments of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
3 Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada
* To whom correspondence should be addressed. E-mail: dingan{at}interchange.ubc.ca.
Given the importance of LPL in cardiac and vascular pathology, the objective of the present study was to investigate whether the
-agonist isoproterenol (ISO) influences cardiac LPL. Incubation of quiescent cardiomyocytes with ISO for 60 minutes 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 AMPK and inactivation of 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
-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.
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