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

Differences in energy metabolism during beta(1) and beta(2)-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 beta(1) compared with beta(2)-AR stimulation may influence the peak functional response and modulation of the response during sustained adrenergic stimulation. Interleaved C-13 and P-31-NMR spectroscopy was used during beta(1) and beta(2)-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 beta(1) than beta(2)-AR stimulation with G (54% vs. 38% reduction P = 0.006) and SF (92% vs. 79% reduction P = 0.04) perfusions. The greater beta(1)-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 beta(1) than beta(2)-AR stimulation. Therefore endogenous glycogen stores are depleted earlier and to a greater extent despite a slightly weaker overall inotropic response during beta(1) than beta(2)-AR stimulation. These findings are consistent with beta(1)-AR-specific PKA-dependent glycogen phosphorylase kinase signaling.