Introduction: The G protein-coupled receptor APJ was paired with its endogenous ligand apelin. Apelin has been shown to produce endothelium-dependent vasodilatation, endothelium-independent vasoconstriction, and to increase force of contraction in the heart in vitro (Maguire et al., 2009). Pulmonary arterial hypertension (PAH) is a serious condition in which pulmonary arterial pressure is increased with death resulting from right heart failure. Evidence suggests that vasodilatation and positive inotropy may be beneficial in PAH (Andersen et al., 2011) and therefore we hypothesised that APJ may be a therapeutic target. The endogenous apelin isoform (Pyr1)apelin-13 has a short half-life, so we have generated a cyclic analogue, MM07, which is equipotent with (Pyr1)apelin-13 in functional studies but more resistant to degradation. The objective was firstly to investigate the expression of apelin and APJ in PAH heart and lung to look for changes with disease. Secondly, to determine the pharmacology of MM07 compared with two endogenous apelin isoforms, (Pyr1)apelin-13 and apelin-36 using a β-arrestin recruitment assay. Methods: Heart and lung tissues were obtained from male Sprague-Dawley rats that had previously been treated with monocrotaline (MCT, s.c. 60mg/kg) (n=4), as a model of PAH, or saline (n=4). 30µm Tissue sections were used for peroxidase-anti-peroxidase and dual-labelling fluorescent immunocytochemistry using apelin and APJ-specific antibodies. Chinese hamster ovary cells artificially expressing the apelin receptor were used to investigate agonist-induced β-arrestin recruitment in a β-galactosidase fragment complementation assay. Concentration-response curves were constructed for (Pyr1)apelin-13 and apelin-36 (both 10-11-10-6M), and MM07(10-8-10-3M). Values of pD2 (-log10 of the agonist concentration producing 50% of the maximum response) were obtained. Results: APJ -like immunoreactivity (LI) was detected in the vascular endothelium and smooth muscle and the myocardium; while apelin-LI localised exclusively to the endothelium in saline and MCT-treated tissues. Specific staining of apelin and APJ appeared to be reduced in endothelium in PAH compared to healthy tissue. Receptor pharmacology revealed that MM07 (pD2=5.8±0.1 SEM, n=6) was less potent than the endogenous agonists (Pyr1)apelin-13 (pD2=8.6±0.01, n=15) and apelin-36 (pD2=8.5±0.01, n=3) at inducing β-arrestin recruitment. Conclusions and Implications: Apelin and the APJ expression was identified in specific cell types of PAH rat heart and lungs. Quantitative measurements are necessary to confirm down-regulation of the apelin system in PAH. Compared to the endogenous apelin isoforms, MM07 was significantly less potent (p<0.05, Student’s t test) as an agonist in the β-arrestin assay. This indicates that MM07 may be a biased agonist as these peptides were equi-effective in vasoconstriction studies.