Atrial natriuretic peptide blocks hemorrhagic brain edema after 4-hour delay in rats.
OBJECTIVE
Atrial natriuretic peptide (ANP) and arginine vasopressin regulate brain water and electrolytes. Treatment with ANP at the onset of a hemorrhagic injury reduces edema. Clinically, however, hemorrhagic masses form too rapidly for preventive treatment. Therefore, we measured the effect of ANP on brain edema after the hemorrhagic mass was formed.


METHODS
Adult rats had hemorrhagic lesions produced by the intracerebral injection of 0.4 U bacterial collagenase. Four hours later, an infusion of ANP (120 or 700 ng/kg per 20 hours) was begun into the peritoneum using an implanted miniosmotic pump. Twenty-four hours after the injury, brain water and electrolyte values were measured. The mechanism of ANP action was explored in other groups of rats that either had osmolality increased with mannitol or were injected with the cyclic GMP analogue, 8-bromo-cGMP.


RESULTS
Atrial natriuretic peptide given after a 4-hour delay significantly reduced brain water and sodium 24 hours after the injury (P < .05). However, neither mannitol nor 8-bromo-cGMP affected brain edema.


CONCLUSIONS
Delayed administration of ANP reduces brain edema secondary to a hemorrhagic mass. Because it is effective after the mass has formed, ANP may be useful in treatment of edema secondary to intracranial bleeding.
Rosenberg
G A
GA
Neurology Services, Veterans Affairs Medical Center, Albuquerque, NM, USA.
Estrada
E Y
EY
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use*; D001921:Brain / Q000503:physiopathology*; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D017364:Collagenases / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D009320:Atrial Natriuretic Factor; D017364:Collagenases