Figure 4: Dabuzalgron Activates ERK, A Canonical Signaling Partner of the α1A-AR

(A) NRVMs were pre-treated with the β-AR antagonist propranolol then exposed for 15 minutes to dabuzalgron. The non-selective α1-AR agonist norepinephrine (NE) was a positive control. Lysates were blotted for total and phospho-ERK (pERK). (B) The EC50 was calculated from 4 concentrations of Dabuzalgron across 5 separate experiments. (C) Summary of pERK/ERK for experiments using 5 different NRVM isolations. The average pERK/ERK ratio (≥2 individual wells) for each experiment was normalized to the pERK/ERK ratio for vehicle-treated NRVMs. (D and E) Mice were treated with DOX, DOX and dabuzalgron, Trm, or DOX, dabuzalgron and Trm for 7 days. Heart lysates were blotted for pERK and ERK. Results were compared using 1-way analysis of variance with Tukey post-test. (F) Mice underwent conscious echocardiography after 7 days of treatment with Trm, DOX and Trm, or DOX, Trm, and dabuzalgron. EC50 = half-maximal effective concentration; NRVM = neonatal rat ventricular myocyte; other abbreviations as in Figures 1, 2, and 3.