HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/E1828    most recent 00288.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by McConville, P. Articles by Spencer, R. G. Search for Related Content PubMed PubMed Citation Articles by McConville, P. Articles by Spencer, R. G.

Greater glycogen utilization during β₁- than β₂-adrenergic receptor stimulation in the isolated perfused rat heart

¹Magnetic Resonance Imaging and Spectroscopy Section, Laboratory of Clinical Investigation, and ²Laboratory for Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Bethesda, Maryland

Submitted 9 May 2007 ; accepted in final form 28 September 2007

Differences in energy metabolism during β₁- and β₂-adrenergic receptor (AR) stimulation have been shown to translate to differences in the elicited functional responses. It has been suggested that differential access to glycogen during β₁- compared with β₂-AR stimulation may influence the peak functional response and modulation of the response during sustained adrenergic stimulation. Interleaved ¹³C- and ³¹P-NMR spectroscopy was used during β₁- and β₂-AR stimulation at matched peak workload (2.5 times baseline) in the isolated perfused rat heart to monitor glycogen levels, phosphorylation potential, and intracellular pH. Simultaneous measurements of left ventricular (LV) function [LV developed pressure (LVDP)], heart rate (HR), and rate-pressure product (RPP = LVDP x HR) were also performed. The heart was perfused under both substrate-free (SF) conditions and with exogenous glucose (G). The greater glycogenolysis was observed during β₁- than β₂-AR stimulation with G (54% vs. 38% reduction, P = 0.006) and SF (92% vs. 79% reduction, P = 0.04) perfusions. The greater β₁-AR-mediated glycogenolysis was correlated with greater ability to sustain the initial contractile response. However, with SF perfusion, the duration of this ability was limited: excessive early glycogen depletion caused an earlier decline in LVDP and phosphorylation potential during β₁- than β₂-AR stimulation. Therefore, endogenous glycogen stores are depleted earlier and to a greater extent, despite a slightly weaker overall inotropic response, during β₁- than β₂-AR stimulation. These findings are consistent with β₁-AR-specific PKA-dependent glycogen phosphorylase kinase signaling.

receptors; adrenergic; metabolism; magnetic resonance spectroscopy