Although the exact mechanisms leading to the augmented cerebral S1P concentrations we observe in our model of hypertension still remain subject of speculation, our results support the involvement of an SphK1-mediated S1P generation as mice lacking this enzyme were protected from the elevation of S1P levels in the brain despite a compensatory up-regulation of SphK2 expression. The gene discussed is SPHK1; the disease is Hypertension.