Angiotensin (Ang) II, a vasoactive peptide and one of the main components of the rennin-angiotensin system (RAS), plays a very significant role in regulating blood pressure and may drive in part, the progression of pulmonary arterial hypertension (1). PAH is caused by functional and structural modifications in the pulmonary vasculature, resulting in increased resistance. This remodeling is accompanied by endothelial dysfunction, smooth muscle cell activation and recruitment of circulating progenitor cells (2). PAH contributes to the development of cardiovascular complications and despite advances in antihypertensive drug therapy, uncontrolled hypertension is still prevalent globally (3). Ang 1- 7, an ACE2 (Angiotensin Converting Enzyme 2)-derived metabolite of Ang II exerts cardioprotective effects and is regarded as a potential antagonist of Ang II (1, 4). Using methods described previously (5), we assessed the mechanism of Ang II–induced Ca2+ signalling in acutely isolated rat pulmonary arterial smooth muscle cells (PASMCs) and the effect of Ang 1-7 on these responses. Extracellular application of 3μM Ang II evoked a robust Ca2+ transient in acutely isolated rat PASMCs, the Fura-2 fluorescence ratio (F340/F380) increasing from 0.44±0.01 to 1.19±0.05 (n=67). Ang II-evoked Ca2+ transients were abolished by the AT1R blocker Losartan (10μM; F340/F380 ratio increasing from 0.68±0.05 to 0.81±0.08 (n=9)), but remained unaffected by the AT2R blocker PD123319 (50μM; F340/F380 ratio increasing from 0.55±0.04 to 1.36± 0.06 (n=9)). Surprisingly, although Ang 1-7 (3μM) had little effect on intracellular calcium in its own right, it significantly attenuated Ang II-evoked Ca2+ transients; Ang II increasing the F340/F380 ratio from 0.46±0.04 to 0.72±0.07 (n=23) in the presence of Ang1-7. We conclude that Ang II induces Ca2+ signals in rat PASMCs by activating AT1Rs and thus induces voltage-gated Ca2+ influx via L-type Ca2+ channels and SR Ca2+ release via RyRs, and in a manner that is be opposed by Ang 1- 7. Gomes et al., 2012 International of Hypertension. Vol 2012, Article ID 493129 1. Gomes et al., 2012 International of Hypertension. Vol 2012, Article ID 493129 Morrell et al., 2009 J. Am Coll. Cardio. Vol 54. S20- S31. Chobanian, 2009 The New England J Med. Vol 361. 878- 887. Grobe et al., 2007. Amer. J. Physiol. Heart Circ Physiol. Vol 292; 736- 742 Kinnear et al., 2004. J Biol Chem Vol 279(52): 54319-26.