Prostanoids generated by the cyclooxygenase (COX) pathway appear to contribute to the neurogenic hypertension (HTN) in rats. The first goal of this study was to establish the time frame during which prostanoids participate in AngII-salt HTN. We induced HTN using AngII (150 ng/kg/min, sc) infusion for 14 days in rats on a high salt (2% NaCl) diet. When ketoprofen pretreatment was combined with treatment during the first 7 days of AngII infusion, development of HTN and increased neurogenic pressor activity (indexed by the depressor response to ganglion blockade) were significantly attenuated for the entire AngII infusion period. This suggest that prostanoid generation caused by administration of AngII and salt leads to an increase in neurogenic pressor activity and blood pressure (BP) via a mechanism that persists without the need for continuing prostanoid input. Second goal of this study was to determine if prostanoid products specifically in the brain contribute to HTN development. Expression of prostanoid pathway genes was measured in brain regions known to affect neurogenic BP regulation. AngII treated rats exhibited changes in gene expression of phospholipase A2 (upregulated in organum vasculosum of the lamina terminalis, paraventricular nucleus, nucleus of the solitary tract, and middle cerebral artery) and lipocalin type prostaglandin D synthase (upregulated in the organum vasculosum of the lamina terminalis). Based on our results we propose that activation of the brain prostanoid synthesis pathway both upstream and downstream from COX at early stages plays an important role in the development of the neurogenic component of AngII-salt HTN.