It is thought that the presence of a phosphatidylinositol-3-kinase (PI3K) dependent Akt signalling in noradrenergic neurones of the brainstem in the spontaneously hypertensive rat (SHR) is responsible for the maintenance of hypertension (Yang & Raizada, 1999). Our aim was to establish whether Akt activity within the rostral ventrolateral medulla (RVLM) contributed to the hypertension in the SHR. We employed real time RT-PCR using unilateral tissue punches containing the RVLM from 16 week old humanely killed SHR and WKY rats, which were used to quantify differences in Akt mRNA expression for all three Akt isoforms (Akt 1, 2 and 3). Using a comparative CT method of calculation, RT-PCR revealed a highly significant 2.4-fold increase (p<0.01) in Akt3 mRNA expression in the SHR (n=5) compared to the WKY (n=6). In contrast, there was no difference in mRNA expression for either Akt1 or Akt2 isoforms between the two rat strains. Double immunofluorescence was employed to reveal co-localisation of phosphorylated Akt (pAkt), which is the active form of Akt, with tyrosine hydroxylase (TH) – a marker for noradrenergic neurones. pAkt expression was found in some TH positive RVLM neurones in both the SHR (n=3) and the WKY (n=3). We conclude that since Akt3 is the major neuronal isoform of Akt, and Akt3 mRNA expression in the RVLM is higher in the SHR, this supports the hypothesis that increased PI3K/Akt signalling in catecholamine neurones contributes to the maintenance of hypertension in the SHR.