Pressor responses to an acute increase in cerebrospinal fluid sodium and exaggeration of the hypertension and sympathetic hyperreactivity in spontaneously hypertensive rats (SHR) by high sodium diet involve release of brain "ouabain" and subsequent activation of the brain renin-angiotensin system. In the present study, we determined whether release of "ouabain" in the median preoptic nucleus participates in these responses. In conscious Wistar rats, the pressor and heart rate responses to central hypertonic saline (0.3 mol/L NaCl, 3.8 microL/min over 10 minutes) and ouabain (0.6 microgram) were compared after median preoptic nucleus injection of either gamma-globulins or Fab fragments binding ouabain and brain "ouabain" with high affinity. Microinjection of Fab fragments into the median preoptic nucleus abolished the pressor and tachycardic responses to central hypertonic saline and significantly reduced the pressor response to central ouabain. In SHR on high sodium, microinjection of Fab fragments into the median preoptic nucleus significantly decreased baseline blood pressure to a level not different from that in SHR on regular sodium (149 +/- 7 versus 145 +/- 5 mm Hg), whereas the enhanced responses to air stress were not affected. Our results support the concept that blood pressure responses to central hypertonic saline and exaggeration of the hypertension in SHR by high sodium diet depend on release of brain "ouabain" in the median preoptic nucleus.