ROLE OF BRAIN OUABAIN-LIKE COMPOUND IN CENTRAL NERVOUS SYSTEM-MEDIATED NATRIURESIS IN RATS

Intracerebroventricular infusion of artificial sodium-rich cerebrospinal fluid induces increases in blood pressure and urinary sodium excretion. To examine the role of brain ouabainlike compound in these central nervous system-mediated responses, we evaluated the effects of prior intracerebroventricular injection of the Fab fragments of digoxin-specific antibody (Digibind, 10 mg/mL, 10 mu L) on changes in blood pressure and urinary sodium excretion after intracerebroventricular infusion of high-sodium (323 mmol/L, 150 mu L/kg per 15 minutes) cerebrospinal fluid in anesthetized rats. Antiouabain action of Digibind was revealed by the inhibition of a contractile response to ouabain in guinea pig aorta. Similar significant increases in blood pressure were found in rats that received preinjection of Digibind (n=14) compared with control rats that received injection of saline (n=5) or normal sheep IgG (n=8). In rats pretreated with Digibind the natriuretic responses to central high sodium were significantly diminished by 68% (P<.05) or 82% (P<.05) compared with rats treated with saline or normal IgG, respectively. In contrast, Digibind did not affect either presser or natriuretic responses to intracerebroventricular angiotensin II (600 ng/30 mu L per 10 minutes). These data indicate that Digibind significantly inhibits increases in renal sodium excretion in response to high central sodium and suggest that brain ouabainlike compound may be involved in central nervous system-mediated natriuresis with nonpressor mechanisms.