Effects of centrally administered arginine vasopressin and atrial natriuretic peptide on the development of brain edema in hyponatremic rats

Objective: Centrally released arginine vasopressin (AVP) and atrial natriur etic peptide (ANP) have been shown to participate in brain volume regulatio n. The aim of the present study was to evaluate the effects of centrally ad ministered AVP and ANP on the time course of development of brain edema in vivo in hyponatremic rats, using diffusion-weighted magnetic resonance imag ing. Methods: We performed intracerebroventricular (ICV) administration of 120 m ug AVP, 20 mug ANP, or physiological saline into the right lateral ventricl e in 18 rats. Twenty-five minutes after the treatment, we induced systemic hyponatremia by the intraperitoneal administration of 140 mmol/L dextrose s olution. Serial diffusion-weighted imaging scans were obtained up to 96 min utes after the start of the hyponatremia. Changes in the brain extra to int racellular volume fraction ratio were estimated as changes in the apparent diffusion coefficient (ADC). Results: No change in the ADC was observed after the ICV injection of salin e or AVP. The onset of hyponatremia induced a rapid and marked ADC reductio n in both groups, indicating an increased intracellular space. However, the ADC decrease became significantly more pronounced in the ICV AVP group (83 .3 +/-4.7% of baseline level, mean standard deviation) than in the saline g roup (93.7 +/-3.3% of baseline, P < 0.001) after 78 minutes of hyponatremia . The ICV injection of ANP induced a prompt ADC increase to 111.5<plus/minu s>10.0% (P<0.05) of the baseline level, indicating a rapid reduction in the intracellular compartment. In the initial phase of hyponatremia, the ADC v alues in the ANP group were consistently higher than those in the saline gr oup, decreasing finally to 86.9<plus/minus>9.6% after 96 minutes of hyponat remia. Conclusion: Our findings demonstrate the opposite effects of AVP and ANP on the intracellular volume fraction of the brain during the development of c ellular brain edema, with an immediate effect on ANP and a delayed effect o n AVP. The results emphasize the direct effects of these hormones on the ce llular volume regulatory mechanisms in the brain during the development of cerebral edema.