Nitric oxide (NO) is the endothelium-derived relaxing factor, which ca
uses relaxation of vascular smooth muscle. NO synthetase, the enzyme f
or the synthesis of NO from its precursor L-arginine, is also widely d
istributed in neurons in the brain, and it has been suggested that NO
may serve as an important neuromodulator. Because NO synthetase is pre
sent in the hypothalamus in relatively high concentration, we have det
ermined whether NO can affect the release of vasopressin in conscious,
chronically prepared rats. The intracerebroventricular (i.c.v.) injec
tion of S-nitroso-N-acetylpenicillamine (12.5 and 25 mug; SNAP), that
spontaneously breaks down to form NO, caused transient dose-related in
creases in the plasma vasopressin concentration of 1 and 2 muU/ml (p <
0.01), respectively. In control experiments in which N-acetylpenicill
amine (25 mug), the precursor for the preparation of SNAP, was injecte
d i.c.v. there was a small, 0.4 muU/ml, increase (p < 0.01) in the pla
sma vasopressin level. The i.c.v. injection of L-arginine (0.5 and 1 m
g), also the precursor for the biosynthesis of NO, resulted in dose-de
pendent increases in the plasma vasopressin concentration similar in m
agnitude to those caused by SNAP. When D-arginine (1 mg), which cannot
serve as a substrate for NO synthetase, was injected i.c.v., there wa
s only a slight delayed increase in the plasma vasopressin concentrati
on. Thus, NO can act centrally to stimulate vasopressin release and ma
y serve as a neuromodulator in the control of vasopressin release.