The neuropeptide apelin and its G-protein coupled receptor, APJ, are expressed in numerous autonomic brain regions, including the parvocellular nucleus of the hypothalamus (PVN) and rostral ventrolateral medulla (RVLM), and are thought to play a role in modulating arterial blood pressure (ABP) by altering sympathetic nerve activity (SNA). Exogenous application of apelin to the PVN and RVLM of anaesthetised rats elevates ABP and SNA, while increased apelin gene expression is observed in the RVLM of spontaneously hypertensive rats (SHRs). This suggests that dysfunction in the central apelinergic system could contribute to the pathophysiology of hypertension. We investigated the role that central APJ plays in the basal control of ABP in the normotensive Wistar Kyoto (WKY) and in the progression of hypertension in the SHR. Values are mean ± SEM, compared by unpaired t-test or one-way ANOVA. Relative expression of the gene for APJ (aplnr) was elevated in the RVLM of SHR compared to WKY (4.2±1.1 vs 1.0±0.2; p<0.05; n=8) and exogenous application of [Pyr1]apelin-13 to the RVLM of sodium pentobarbital (50mg.kg-1 i.p.) anaesthetised rats caused a greater increase in mean ABP (MABP), recorded via femoral artery catheter, in SHR compared to WKY (20±2mmHg vs 10±2mmHg; p<0.01; n=8) thus suggesting an enhancement of the apelinergic system in hypertensive rats. To further investigate this WKY (n=12) and SHR (n=12) were chronically implanted with blood pressure radiotelemeters under isoflurane anaesthesia (2% in O2). After a 5-day baseline period rats were anaesthetised with a mixture of ketamine (60mg.kg-1) and medetomidine (250µg.kg-1, both i.m.) prior to bilateral RVLM microinjection with a lentiviral APJ-specific-shRNA construct. 25 days after lentivirus injection, RVLM aplnr expression was decreased in APJ-shRNA-injected compared to scrambled-shRNA- injected rats (0.5±0.1 vs 1.1±0.1; p<0.001; n=24) and increases in MABP associated with exogenous injection of [Pyr1]apelin-13 to the RVLM were abolished (10±1mmHg vs -2±1mmHg; p<0.001). 25 days after virus injection MABP was unchanged relative to baseline in scrambled- and APJ-shRNA-injected WKY (2±1 vs 3±7mmHg) and SHR (10±4 vs 7±8mmHg). Additionally, spectral analysis of BP revealed no changes in low frequency systolic BP variability between scrambled- or APJ-shRNA-injected WKY or SHR, thus suggesting that sympathetic vasomotor tone was unaffected by RVLM aplnr knock-down. Therefore, these data imply that endogenous apelin, acting via APJ in the RVLM, does not play a role in maintaining basal BP in WKY rats or in the genesis of hypertension in the SHR.