Increased phosphatidylinositol-3,4,5-triphosphate (PIP₃) signalling is thought to be responsible for the augmented catecholamine release induced by angiotensin II in the brainstem of spontaneously hypertensive rats (SHR) (1). This increase in catecholaminergic signalling is thought to result in hypertension. Supporting this idea, inhibition of phoshoinositide-3-kinase (PI3K) in the rostral ventrolateral medulla (RVLM) reduced blood pressure in SHR but had no effect in the Wistar-Kyoto (WKY, normotensive control) (2). Elevated PIP₃ levels could result from an increase in the expression of PI3K enzymes or a decreased expression of PIP₃ metabolising enzymes; phoshoinositide-lipid-3-phosphotase (PTEN) and SH2-containing inositol phosphatase 1 and -2 (SHIP, 5- and 3-phosphotases, respectively). We sought to determine whether the mRNA levels of the G-protein activated PI3K subunits, p110γ and p101 as well as PTEN, SHIP1 and SHIP2 are altered in SHR medullary catecholaminergic nuclei. Total RNA was extracted from micropunches of C1/RVLM, A1/caudalVLM and A2/NTS regions of neonatal SHR and WKY (n=22; rats were humanely killed). Expression levels were assessed by real time RT-PCR based on the cycle threshold difference (ΔCt) method using GAPDH as the reference gene. SHIP2 mRNA levels were 2.3-fold lower in SHR than in WKY (p=0.009, unpaired t test, ΔCt = 8.16 ± 0.24 ; n = 11 vs 6.95 ± 0.39; n = 10, mean ± S.E.M.) in the C1/RVLM region but no difference was observed in the A1 or A2 areas. In all the regions tested, no significant differences in p110γ, p101, PTEN or SHIP1 mRNA levels were found between WKY and SHR. This data implies that differences in PIP₃ signalling between SHR and WKY might be at least in part, related to decreased expression of SHIP2 in the C1/RVLM region, an area previously implicated in the generation of PIP₃-dependent hypertension (2). Presumably, decreased SHIP2 activity would increase PIP₃ levels resulting in abnormal catecholaminergic signalling and hypertension. As SHIP2 converts PIP₃ to PI(3,4)P₂ the possibility that PI(3,4)P₂ levels may be important in maintaining normal catecholaminergic signalling must also be considered.