Biventricular Differences In Beta-Adrenergic Receptor Signaling Following Burn Injury

Burn injury detrimentally affects the myocardium, primarily due to over-activation of P-adrenergic receptors (beta-AR). Autopsy reports from our institution reveal that patients often suffer from right ventricle (RV) failure. Since burn injury affects beta-AR signaling in the left ventricle (LV), we proposed that beta-AR signaling may also be altered in the RV. A rodent model with a scald burn of 60% of the total body surface area was used to test this hypothesis. Ventricles were isolated 7 days post-burn. We examined the expression of p-ARs via Western blotting and the mRNA expression of downstream signaling proteins via qRT-PCR. Cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) activity were measured in membrane and cytosolic fractions, respectively, using enzyme immunoassay kits. beta(1)-AR protein expression was significantly increased in the RV following burn injury compared to non-burned RV but not in the LV (p = 0.0022). In contrast, beta(2)-AR expression was unaltered among the groups while G(ai) expression was significantly higher in the LV post-burn (p = 0.023). B-arrestin-1 and G-protein coupled receptor kinase-2 mRNA expression were significantly increased in the left ventricle post-burn (p = 0.001, p<0.0001, respectively). cAMP production and PKA activity were significantly lower in the LV post-burn (p = 0.0063, 0.0042, respectively). These data indicate that burn injury affects the beta-AR signaling pathway in the RV independently of the LV. Additionally, non-canonical beta-AR signaling may be activated in the RV as cAMP production and PKA activity were unchanged despite changes in beta(1)-AR protein expression.