In ischemia, cardiac sympathetic nerve endings (cSNE) release excessive amounts of norepinephrine (NE) via the non-exocytotic Na⁺-dependent NE transporter (NET). NET, normally responsible for NE re-uptake into cSNE, reverses in myocardial ischemia, releasing pathologic amounts of NE. This carrier-mediated NE release can be triggered by elevated intracellular Na⁺ levels in the axoplasm. That ischemia activates the pH_i regulatory Na⁺/H⁺ exchanger (NHE) in cSNE is pivotal in increasing intraneuronal Na⁺ and thus, activating carriermediated NE release. Angiotensin (ANG II) levels are also significantly elevated in the ischemic heart. Yet, the effects of ANG II on cSNE, which express the ANG II receptor, AT₁R, are poorly understood. We hypothesized that ANG II-induced AT₁R activation in cSNE may be positively coupled to NHE activity and thereby facilitate the pathologic release of NE associated with myocardial ischemia. We tested this hypothesis in human neuroblastoma cells, an optimal cSNE model, stably transfected with rat AT_1AR (SH-SY5Y-AT_1A). SH-SY5Y-AT_1A constitutively express amiloride-sensitive NHE and the NET. NHE activity was assayed in BCECF-loaded SHSY5Y-AT_1A as the rate of the Na⁺-dependent alkalinization in response to an acute acidosis. ANG II activation of AT_1AR markedly increased NHE activity in SH-SY5Y-AT_1A via a Ca⁺⁺-dependent pathway, and promoted carrier-mediated NE release. Additionally, in guinea pig cSNE expressing native AT₁R, ANG II elicited carrier-mediated NE release. In SH-SY5Y-AT_1A and cSNE, amiloride inhibited the ANG II-mediated release of NE. Our results provide a link between AT₁R and NHE in cSNE which can exacerbate carrier-mediated NE release during protracted myocardial ischemia.