High sodium intake (HNa) increases brain ouabainlike activity (OLA) in rats. In spontaneously hypertensive rats (SHR), HNa exaggerates development of hypertension and pressor and sympathoexcitatory responses to stress. To investigate whether dietary sodium-induced changes in brain OLA play a functional role, responses of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to intracerebroventricular ouabain and to mental stress and intracerebroventricular α2-adrenoceptor agonist guanabenz alone or preceded by intracerebroventricular ouabain were recorded in conscious SHR and Wistar-Kyoto (WKY) rats maintained from 4 to 8 weeks of age on different sodium diets: 1) low sodium intake (LNa, 17 μmol), 2) normal sodium intake (NNa, 101 μmol), and 3) HNa (1,370 μmol). SHR on NNa showed significantly higher MAP and RSNA compared with WKY rats on NNa. HNa or LNa significantly increased or decreased MAP but had no effects on resting RSNA in SHR and had no effects on resting MAP and RSNA in WKY rats. Intracerebroventricular ouabain induced dose-dependent increases in MAP, RSNA, and HR. In both SHR and WKY rats, LNa significantly enhanced these responses. In contrast, HNa significantly attenuated these responses only in SHR. Air stress increased and intracerebroventricular guanabenz decreased MAP, HR, and RSNA. The magnitudes of increases and decreases were significantly larger in SHR than in WKY rats. In WKY rats, dietary sodium did not change these responses. In contrast, in SHR, HNa significantly enhanced MAP, HR, and RSNA responses to air stress or intracerebroventricular guanabenz. In SHR on LNa and NNa, intracerebroventricular preinjection of ouabain enhanced the MAP, HR, and RSNA responses to air stress or intracerebroventricular guanabenz and equalized them to those in SHR on HNa. In WKY rats, preinjected ouabain did not affect responses to air stress or guanabenz. These results suggest that HNa increases brain OLA, thus decreasing responses to exogenous ouabain and that, considering its interaction with air stress and central α2-adrenoceptor stimulation, brain OLA may be involved in the central effects of dietary sodium in SHR, without exerting these effects in WKY rats, thus contributing to the differential pressor and sympathoexcitatory responses to HNa in SHR versus WKY rats.