Either V1AR overexpression or stimulation can block ISO-mediated cardiac contractility ex vivo, even in the presence of genetic Gq protein inhibition. Cardiac contractile parameters were measured in ex vivo Langendorff preparations from WT or V1AR-TG mice. Infusion of increasing concentrations of ISO led to an increase in contractility in WT hearts as measured by LVDP (A), +dP/dt (B) and -dP/dt (C), expressed as % of baseline. These effects were blocked in V1AR-TG hearts, in WT hearts pretreated with AVP (1 nM) and in GqI-expressing hearts pretreated with AVP. *p<0.05, **P<0.01, ***p<0.001 versus WT+AVP, †p<0.05, ††p<0.01, †††p<0.001 versus V1AR-TG, and ‡‡p<0.01, ‡‡‡p<0.001 versus GqITG+AVP at corresponding concentration, two-way repeated measures ANOVA with Bonferonni multiple comparisons test (6 comparisons total). N = 5 (WT+Veh), 5 (WT+AVP), 8 (V1AR-TG), 7 (GqI-TG+AVP) hearts each.