Introduction: Apelin is the endogenous ligand of the G protein-coupled receptor APJ. In human cardiovascular tissues apelin produces endothelium-dependent vasodilatation and positive inotropy in vitro, and (Pyr1)apelin-13 is the predominant isoform of mature apelin in the heart(1). Beneficial roles for both apelin and ACE2, that converts angiotensin-II to angiotensin(1-7), have been reported in pulmonary arterial hypertension (PAH)(2,3,4). Intriguingly, ACE2 also removes the C terminal phenylalanine from (Pyr1)apelin-13, generating (Pyr1)apelin-13(1-12)(5). Aims and Hypotheses: Our aim was to investigate whether (Pyr1)apelin-13(1-12) is present endogenously in normal and PAH rat and human cardiopulmonary tissues, and to test our hypothesis that this metabolite retains significant biological activity. Methods: Specific (Pyr1)apelin-13(1-12) and ACE2 antibodies were used in peroxidase-anti-peroxidase and dual-labelling fluorescent immunocytochemistry experiments. 30µm sections of cardiopulmonary tissues were from normal and PAH human heart and lung (n=4 for each) and from healthy male Sprague-Dawley rats and rats treated with monocrotaline (60mg/kg s.c.), as a model of PAH (n=4 for each). Biological activity of (Pyr1)apelin-13(1-12) was determined in β-arrestin recruitment and receptor internalisation assays, and compared to (Pyr1)apelin-13 (10-11-10-6M ; n=3-12). Values of pD2 (negative log10 of the concentration producing 50% of maximum response) and maximum responses were determined using GraphPad Prism. Results: In both rat and human tissues, (Pyr1)apelin-13(1-12)-like immunoreactivity(-LI) was present in the endothelium of normal heart and lung and PAH heart and co-localized with ACE2-LI, but was reduced or absent in PAH lung from both species. Furthermore, (Pyr1)apelin-13(1-12) exhibited full agonist activity with 5-10 fold lower potency in β-arrestin recruitment (pD2= 7.84±0.07) and receptor internalisation assays (pD2= 8.39±0.01) compared to (Pyr1)apelin-13 (pD2= 8.76±0.09, pD2= 8.82±0.01, respectively). Conclusions: This study demonstrates for the first time that (Pyr1)apelin-13(1-12) can be detected in rat and human cardiopulmonary tissues and is present in cells that also express ACE2. Our functional data suggest that ACE2 does not inactivate (Pyr1)apelin-13, rather the metabolite retains a biological activity comparable to the parent peptide. If the apelin system is beneficial in PAH, it is possible that the observed reduction in (Pyr1)apelin-13(1-12) expression in PAH lung may contribute to the pathogenesis of the disease, and generation of (Pyr1)apelin-13(1-12) may therefore also contribute to the positive actions of ACE2 therapies.