Differential effects of atrial natriuretic peptide on the brain water and sodium after experimental cortical contusion in the rat.
Atrial natriuretic peptide (ANP) plays an important role in the regulation of water and sodium in the body via cyclic GMP (cGMP) pathway. Although ANP has been shown to be protective in cerebral ischemia or intracerebral hemorrhage, its role in traumatic brain injury (TBI) has yet to be elucidated. We herein assessed ANP effects on brain water and sodium in TBI. Controlled cortical impact (3 mm depth, 6 m/sec) was used to induce an experimental cortical contusion in rats. Continuous administration of ANP 0.2 (n = 6) or 0.7 microg/kg/24 h (n = 6), cGMP analogue (8-Bromo-cGMP) 0.1 (n = 5) or 0.3 mg/kg/24 h (n = 5), or vehicle (n = 6) was begun 15 minutes after injury, using a mini-osmotic pump implanted into the peritoneal cavity. At 24 hours after injury, ANP significantly exacerbated brain edema in the injured hemisphere in a dose-dependent manner while it reduced brain sodium concentrations in both hemispheres. These ANP effects could be mimicked by a cGMP analogue. In the second series (n = 20), BBB integrity was assessed by evaluating the extravasation of Evans blue dye. ANP or cGMP analogue significantly worsened BBB disruption in the injured hemisphere at 24 hours after injury. These findings suggest that ANP administration exacerbates brain edema after the experimental cortical contusion in rats, possibly because of an increase in the BBB permeability via cGMP pathway, whereas it reduces brain sodium levels.
Fukui
Shinji
S
Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, 23298, USA.
Fazzina
Giovanna
G
Amorini
Angela M
AM
Dunbar
Jana G
JG
Marmarou
Anthony
A
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects; D001835:Body Weight; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism*; D004396:Coloring Agents / Q000493:pharmacokinetics; D006152:Cyclic GMP / Q000378:metabolism; D004573:Electrolytes / Q000097:blood; D005070:Evans Blue / Q000493:pharmacokinetics; D007274:Injections, Intraperitoneal; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D014867:Water / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects
D004396:Coloring Agents; D004573:Electrolytes; D014867:Water; D005070:Evans Blue; D009320:Atrial Natriuretic Factor; D012964:Sodium; D006152:Cyclic GMP; D011188:Potassium