Cardiovascular responses to icv hypertonic saline involve angiotensin II (AII) and "ouabain" in the median preoptic nucleus (MnPO)

Icv administration of either Fab fragments binding brain "ouabain" and related steroids with high affinity or Losartan blocks cardiovascular responses to icv hypertonic saline (HS) and ouabain. Since the MnPO contains both "ouabain" and All positive axons, the purpose of the present study was to determine whether these two neuromodulators in the MnPO are involved the cardiovascular responses to icv HS and ouabain. Experiments were performed in conscious, normotensive Wistar rats chronically instrumented with MnPO guide cannulae and arterial and venous catheters At the beginning of the experiment rats were injected into the MnPO in series I with γ-globulins (day I) and Fab fragments (17μg in 200nl) (day 2) and in series 2 with artificial CSF or Losartan (5μg) (randomized between day 1 and day 2). Subsequently, they were infused icv with HS (0.3M 3.8μl/min for 10 min). After the pressor response to HS had subsided, 0.6 μg of ouabain was injected icv. In control conditions both HS and ouabain significantly increased MAP and HR. Pretreatment with Fab fragments significantly attenuated pressor and HR response to icv HS (20±2 vs 10±2 mmHg P<0.05) and pressor response to icv ouabain (19±2 vs 8±2 mmHg P<0.05). After MnPO injection of Losartan both pressor and HR responses to icv HS were not different from those in volume control experiment (5±1 vs 6±3 mmHg NS) and responses to icv ouabain significantly attenuated (14±1 vs 8±1 mmHg P<0.05). Our results suggest that both MnPO "ouabain" and All are invoked in the cardiovascular responses to an increase in CSF sodium.