Stimulation of brain Na⁺ channels by Phe-Met-Arg-Phe-NH₂ (FMRFamide) increases sympathetic nerve activity and blood pressure (BP) in Wistar rats. Blockade of brain ouabain-like compounds (OLC) by specific antibody Fab fragments prevents these responses to icv FMRFamide. In the present study, we evaluated the effects of high salt intake on brain FMRFamide levels and the responses of BP and brain OLC to intracerebroventricular (icv) infusion of FMRFamide in Dahl salt -sensitive (S) and -resistant (R) rats. FMRFamide and OLC content were measured by radioimmunoassy (RIA) and enzyme-linked immunosorbent assay (ELISA), respectively. High salt intake (1370 µmol Na⁺/g food) for 2 weeks significantly increased BP in Dahl S, but not in Dahl R rats. On regular salt diet, Dahl S and Dahl R rats showed similar FMRFamide levels in the whole hypothalamus, pons & medulla, and spinal cord. High salt diet for two weeks did not affect FMRFamide levels in these tissues in both Dahl S and R rats. In Dahl S, but not in R rats, chronic icv infusion of FMRFamide (200 nmol/kg/day) for two weeks significantly increased BP (MAP: 116 ±5 mmHg vs 100 ± 2 mmHg, p<0.01). Chronic icv infusion of FMRFamide significantly increased hypothalamic and pituitary OLC in Dahl S, but not R rats. These results indicate that Dahl S rats exhibit enhanced central responses to FMRFamide. In Dahl S, but not in R rats, on high salt diet enhanced Na⁺ entry through FMRFamide-activated brain Na⁺ channels may increase brain OLC release, thereby leading to hypertension.