Angiotensin (Ang) II, the main effector of the renin-angiotensin system, is one of the major mediators of vascular remodeling in hypertension. Besides being a potent vasoactive peptide which also acts on vasopressin neurons in the hypothalamus, Ang II was shown to induce cytokines and chemokines such as MCP-1/CCL2, IL-6 and IL-8 via the AT1 receptor (Funakoshi, Y. et al. Hypertension, 2001). Chemokines are small secreted proteins originally defined as chemoattractants for leukocytes. Recent evidence has established that they are expressed in the central nervous system where they are involved in inflammatory processes, ontogenesis, intercellular communication and may play a critical role at multiple stages in atherosclerosis, including the initiation of the fatty streak, promotion of plaque instability, and remodeling after myocardial infarction (De Lemos JA et al Circulation, 2003). We have provided evidence that some chemokines such as MCP-1/CCL2 or SDF-1/CXCL12 and its receptor CXCR4 are constitutively and regionally expressed in specific neuronal populations throughout regions of the adult rat brain, in particular in the hypothalamus. In the hypothalamus, we have found that both MCP-1/CCL2 SDF-1/CXCL12 are co-localized in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) exclusively with vasopressin neurons (Banisadr et al, Eur J Neuroscience 2003; J Comp Neurol. 2005). SDF-1/CXCL12 is able to inhibit (Ang)II induction of vasopressin and is involved in the electrical activity and physiological regulation of vasopressin neurons (Callewaere et al PNAS, 2006). The Brattleboro rat is known to present diabetes insipidus due to a marked defect in the regulation of vasopressin gene expression and consequently lacks the ability to synthesize vasopressin. We investigated the distribution of SDF-1/CXCL12 and CXCR4 immunoreactivity in homozygous (di/di) and heterozygous (di/+) Brattleboro in comparison with control Long Evans (LE) rats. We show by dual fluorescent immunohistochemistry that SDF-1/CXCL12 and CXCR4 are dramatically decreased in the Brattleboro rats as compared to their expression in LE. This decrease in SDF-1/CXCL12 and CXCR4 immunoreactivity is strictly correlated with the decrease in vasopressin expression in PVN and SON of Brattleboro rats since in heterozygous animals which express arginine vasopressin at a lower level than LE, SDF-1/CXCL12 and CXCR4 are proportionally decreased in comparison to the vasopressin levels. To test whether such decrease in SDF-1/CXCL12 and CXCR4 is due to a central effect, we treated homozygous Brattleboro rats with dDAVP, an analog of vasopressin, in order to restore the vasopressinergic renal function of these animals. Under these conditions, SDF-1/CXCL12 and CXCR4 immunoreactivity remains at the low level observed in the Brattleboro rat, suggesting a central deficit in SDF-1/CXCR4 expression. These original findings suggest that the chemokinergic systems such as SDF-1/CXCL12 can be involved in the modulation of vasopressin-mediated neuroendocrine functions.