Sleep apnoea is commonly associated with co-morbidities including hypertension with elevated sympathetic nerve activity (SNA). Activation of the renin-angiotensin system (RAS) is thought to be a mechanism involved in the pathogenesis of hypertension is sleep apnoeics. The intermittent hypoxia experienced in sleep apnoea is thought to contribute to the activation of the SNA, contributing to the development of hypertension. We have reported that acute intermittent hypoxia (AIH, 10x45s of 10% O2, separated by 5mins hyperoxia) elicits a sustained elevation of splanchnic SNA in the anaesthetized rat (Xing & Pilowsky, 2010). The aim of the present study was to examine the role of the renin-angiotensin system in the sustained elevation of SNA, termed sympathetic long-term facilitation (LTF) in anaesthetised (urethane, 1.5g/kg, i.p.), vagotomised, paralysed (pancuronium, induction dose 0.8mg/kg, continuous infusion 0.4mg/hr) and ventilated Sprague-Dawley rats (Xing & Pilowsky, 2010). The greater splanchnic nerve, the renal sympathetic nerve, and the phrenic nerve were continuously recorded during and for at least an hour after AIH. AIH evoked LTF in the splanchnic (+63±8.5% above baseline, n=6) and renal sympathetic nerves (+38±9.7% above baseline, n=6). Pretreatment before AIH with an angiotensin 1A receptor blocker, valsartan (0.1mg/kg, i.v.) abolished the sympathetic LTF in the splanchnic nerve (+2±9.5% above baseline, n=7). Intermittent injections of angiotensin II (10x35pmol in 0.1ml, i.v., 5mins intervals) also elicited sympathetic LTF (+42.4 ±11.5% above baseline, n=5). Intermittent phenylephrine injections (10x 25µg in 0.1mL, i.v.), resulting in intermittent renal hypoperfusion also produced sympathetic LTF (+72.4±21.6% above baseline, n=5), that was abolished by pretreatment with the renin inhibitor, aliskiren (1mg/kg, i.v., n=4). Continuous infusion of the equivalent dose of angiotensin II (350pmol in 1mL) or phenylephrine (250µg in 1mL) over 10 mins, did not cause sympathetic LTF. This data supports the idea that activation of the RAS is sufficient for the development of sympathetic LTF following AIH. In addition, the temporal nature of intermittent activation of RAS is required for sympathetic LTF. This data is in agreement with data in human studies that AIH activates angiotensin type I receptors to increase arterial blood pressure (Foster et al., 2010), and suggests that activation of RAS may be relevant to sympathetic overactivity and hypertension in sleep apnoea patients.