EVIDENCE THAT NITRIC-OXIDE CAN ACT CENTRALLY TO STIMULATE VASOPRESSINRELEASE

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.