Neurogenic hypertension (HTN) is characterized by increased sympathetic activity, but the specific causes remain to be determined. Using the angiotensin II-high salt model (AngII-salt) of neurogenic HTN in rats, we observed that chronic central prostaglandin D synthase (L-PGDS) inhibition caused attenuation of HTN development and neurogenic pressor activity. As L-PGDS promotes prostaglandin D2 (PGD2) synthesis in the brain, we hypothesized that increased PGD2 levels acting on DP-1 receptors in key cardio-regulatory brain regions participate in AngII-salt HTN development. To test this hypothesis adult male Sprague Dawley rats on high salt (2% NaCl) diet received either vehicle or angiotensin II (150ng/kg/min, sc.), using a mini-osmotic pump. On day 4, the developmental stage of HTN, brains from 5 control and 5 AngII treated rats were collected for PGD2 measurement using liquid chromatography coupled with mass spectrometry. In another set of control and treated rats, brains were perfusion fixed and then collected for DP1R expression measurement in neurons using immunofluorescence. We found that AngII-salt treated rats had significantly increased PGD2 levels (34.5±13.4ng/region) in the rostral ventrolateral medulla (RVLM) compared to vehicle-treated rats (12.4±4.8ng/region; p<0.05). Relative expression of neuronal DP1 receptors in RVLM was less in AngII-salt treated rats (163.8±11.1 relative intensity units) than that of the control rats (200.6±14). Similar changes were not seen in any other brain region. These data suggest that AngII and salt increase PGD2 in the RVLM that acts on neuronal DP1 receptors to cause sympathoexcitation and hypertension.