Figure 1.

Sustained Crhr2 activation induces cardiac dysfunction. (A) G-protein–coupled receptor (GPCR) gene expression analysis in isolated cardiomyocytes 2 wk after transverse aortic constriction (TAC) using qRT-PCR greater than five copies per ng of RNA. The results are representative of two independent experiments. (B) Protein expression of Crhr2, adrenoceptor β-1 receptor (Adrb1), and prostaglandin E receptor 1 (Ptger1) in left ventricles 2 wk after sham or TAC was determined by immunoblotting analysis. (C) Statistical evaluation of (B; sham set to 1; n = 3; two-tailed Student’s t test). (D) Plasma Ucn2 concentration 2 wk after sham or TAC (n = 17; two-tailed Student’s t test). (E) Crhr2 tissue distribution in humans. (F and G) Plasma Ucn2 concentration (F), and cardiac morphology, left ventricular weight/tibia length (LVW/TL) ratio (G) after 4 wk of sustained Ucn2 infusion (n = 5; two-way ANOVA and Bonferroni post-hoc test). (H) Left ventricular fractional shortening determined by echocardiogram after 4 wk of sustained Ucn2 infusion (n = 5; two-tailed Student’s t test). (I) Systolic blood pressure after 4 wk of sustained Ucn2 infusion (n = 5; two-tailed Student’s t test). (J) Plasma BNP concentration after 4 wk of sustained Ucn2 infusion (n = 5, 2-tailed Student’s t test). Error bars indicate SEM. *, P < 0.05; **, P < 0.01; ns, not significant. The results are representative of three independent experiments (B–J).

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