Cardiomyocyte-specific, Crhr2-deficient mice exhibit suppressed pressure overload–induced cardiac dysfunction. (A) Protein extracts from isolated cardiomyocytes of vehicle- or tamoxifen-treated α-myosin heavy chain (αMHC)-CreERT2 (Cre)-negative and -positive Crhr2^flox/flox mice were blotted with antibodies against Crhr2 and actin. (B and C) LVW/TL ratio (B) and left ventricular fractional shortening (C) 4 wk after continuous infusion of Ucn2 or vehicle (sham) through an osmotic pump (n = 6; two-way ANOVA and Bonferroni post-hoc test). (D) LVW/TL ratio 4 wk after transverse aortic constriction (TAC; n = 6–10; two-way ANOVA and Bonferroni post-hoc test). (E) Fibrotic changes in left ventricles 4 wk after TAC were assessed by PicroSirius red staining (n = 4; two-way ANOVA and Bonferroni post-hoc test). (F and G) Left ventricular fractional shortening (F) and left ventricular end-diastolic dimension (G) were assessed by echocardiogram before and 4, 12, and 24 wk after TAC (n = 6; two-way ANOVA and Bonferroni post-hoc test). (H) Survival plot for control mice and cmc-Crhr2-KOs up to 8 mo after TAC (n = 36–37; Log-rank test). Error bars indicate SEM. *, P < 0.05; **, P < 0.01; ns, not significant. The results are representative of three independent experiments (A–G).