FIGURE 4.

Gq coupling is required for cardioprotection by an α1A agonist in vitro with doxorubicin, and in vivo with transverse aortic constriction (TAC). A: Cultured WT or GqKI AMVMs were treated 24 h with doxorubicin (DOX, 5 μM), in the presence of A61603 (A6, 100 nM) or Vehicle. Cell survival was quantified by the MTT assay for viable mitochondria. Values are percent increase in MTT with A6 vs. vehicle; each point is a culture from a different heart, with 2–3 35mm dishes for each group in each culture, with MTT read in triplicate; p by unpaired t test. B: Adult male mice had TAC to create a gradient ~110 mmHg; survival over 2 weeks was 98% in WT and 64% in GqKI; p value by Gehan-Beslow-Wilcoxon test. C. At 2 weeks after TAC, when fractional shortening (FS) by echo had dropped from baseline 62±1% to an average 40±1% (n=17), WT mice and surviving GqKI mice were treated with A6 10 ng/kg/d by osmotic minipump. In WT mice, A6 for 2 more weeks increased FS by 24%, to 50±2%, or 82% of baseline. In GqKI mice treated with A61603, FS fell further (−11%), the same as WT mice treated with vehicle (−10%). Values are percent change in FS for the same mouse with treatment between 2 weeks and 4 weeks; p by ordinary one-way ANOVA with Tukey’s multiple comparisons test. Complete echo data are in Online Table I and Online Figure IV