Junctional adhesion molecule-1(JAM-1, or the F11 receptor) is a transmembrane protein located at the inter-cellular junctions of endothelial and epithelial cells. Up regulation of JAM-1 was previously reported in the brainstem of the spontaneously hypertensive rat (SHR), which preceded the development of hypertension and was localised to the microvasculature (Waki et al. 2007). Here, we sought to further investigate the role of JAM-1 in the development of hypertension in both the ANG II infusion and SHR animal models, and tested the hypothesis that angiotensin II (ANG II) drives JAM-1 expression. Wistar rats were anaesthetized by intraperitoneal injection of a mixture of ketamine hydrochloride (50%), medetomidine hydrochloride (30%) and implanted with radio-transmitters for chronic measurement of arterial blood pressure. They were also implanted with Alzet osmotic mini pumps for chronic intracisternal infusion of ANG II at 5ng/kg/min. A control group of rats were infused with saline. The 24h mean arterial pressure (MAP) of Wistar rats infused with ANG II was not higher than that of the saline treated group until day 10 (saline: 95±2 mmHg vs ANG II: 104±3 mmHg; mean±SEM, P<0.05). JAM-1 mRNA level, determined by real-time RT-PCR, in nucleus tractus solitarii (NTS), rostral ventrolateral medulla (RVLM) and paraventricular nuclei (PVN) was raised (by 1.78±0.09, 1.66±0.08 and 1.81±0.06 fold respectively) compared with control at day 10 (P<0.01, N=4). Although MAP was not different to control at day 5, JAM-1 mRNA was already up regulated in the ANG II infused rat group by 1.40±0.07, 1.46±0.07 and 1.43±0.13 fold in NTS, RVLM and PVN respectively (P<0.05, N=4). Western blot revealed that compared to control, JAM-1 protein levels were also significantly elevated at both 5 and 10 days after ANG II infusion in all tested tissues (e.g. brainstem microvessel, lung, liver, kidney, spleen and heart). In the SHR, blockade of ANG II type 1 receptor (AT1R; Losartan 30mg/kg/day in drinking water for 4 weeks) reduced the high level of JAM-1 characteristic of this rat strain (Waki et al. 2007) from 193±14 mmHg to 126±8 mmHg (P<0.01). Losartan also decreased JAM-1 mRNA levels in NTS, RVLM and PVN by 0.57±0.13, 0.49±0.12 and 0.39±0.14 fold respectively (P<0.05, N=4). Western blot analysis confirmed that JAM-1 protein levels were decreased in brainstem blood vessel, lung, liver, kidney, spleen and heart. We conclude that systemic over-expression of JAM-1 at both pre-hypertensive and hypertensive states may be driven by increased activity of the renin-angiotensin system at the levels of the tissues and circulation. Because up regulation of JAM-1 precedes measurable elevation of BP in various animal models, JAM-1 could become a clinically useful early diagnostic marker for the risk of developing hypertension.