Apelin and its receptor are emerging as an endogenous counter-regulator of the renin-angiotensin-aldosterone system. In experimental models, apelin opposes angiotensin II (Ang II)-mediated hypertension and cardiovascular fibrosis as well as the acceleration of atherosclerosis and the development of abdominal aortic aneurisms. In vitro studies show that apelin antagonizes Ang II signaling through the Ang II Type 1 receptor (AT1), but the precise molecular mechanism has not been elucidated. In the present study, we sought to test the hypothesis that the apelin receptor is a dominant negative regulator of AT1. Using co-immunoprecipitation and bioluminescence resonance energy transfer (BRET) techniques, we confirm that the apelin receptor (APJ) and AT1 physically interact to form a heterodimeric complex. The interaction between APJ and AT1 was increased by the APJ agonist apelin-13 (Ap13), but not Ang II. Ap13-mediated dimerization between APJ and AT1 eliminated Ang II-mediated recruitment of β-arrestin to AT1 and significantly decreased Ang II-induced Ca 2+ flux. Radioligand binding studies revealed that Ap13 reduced Ang II binding without direct competition. Taken together, these data lead us to conclude that apelin counter-regulates the renin-angiotensin-aldosterone system through the apelin-dependent heterodimerization and APJ-mediated negative allosteric regulation of AT1 function.