V1AR antagonist SR 49059 protects against TAC-induced cardiac dysfunction. In response to TAC, fractional shortening (A) and ejection fraction (B) were significantly decreased in vehicle-treated mice (TAC+V) compared to vehicle-treated sham surgery mice (Sham+V), effects prevented with SR 49059 (1mg/kg/day, starting 1 week post-TAC). ††p<0.01, †††p<0.001 versus Sham+V, *p<0.05, **p<0.01 versus TAC+SR at corresponding weeks, twoway repeated measures ANOVA with Bonferroni multiple comparisons test (6 comparisons total). N = 9 (Sham+V), 8 (Sham+SR), 13 (TAC+V), 14 (TAC+SR). As shown by radioligand binding analysis, TAC increases V1AR membrane density (C, N = 7 (Sham+V), 4 (Sham+SR), 7 (TAC+V), 5 (TAC+SR)) and decreases βAR membrane density (D, N = 4 (Sham+V), 4 (Sham+SR), 6 (TAC+V), 6 (TAC+SR)), effects prevented by treatment with SR 49059. *p<0.05, **p<0.01, ns = not significant, Exact Wilcoxan Rank-Sum Test.