Neuronal nitric oxide synthase gene inactivation reduces the expression of vasopressin in the hypothalamic paraventricular nucleus and of catecholamine biosynthetic enzymes in the adrenal gland of the mouse.

The impact of a lifelong absence of the neuronal nitric oxide synthase (nNOS) in the neuroendocrine stress response was investigated in nNOS knockout (KO) and wild type (WT) mice under basal conditions and in response to forced swimming. In the hypothalamic paraventricular nucleus oxytocin and corticotropin-releasing-hormone mRNA levels did not differ between these genotypes under resting conditions, whereas vasopressin mRNA levels were significantly lower in nNOS KO than in WT animals. Also, in the adrenal glands basal levels of tyrosine hydroxylase protein, the rate-limiting enzyme for catecholamine biosynthesis, and of phenylethanolamine N-methyltransferase, which converts norepinephrine to epinephrine, were significantly reduced in nNOS KO mice. Plasma adrenocorticotropin, corticosterone, norepinephrine and epinephrine levels were similar in the KO and WT genotypes under resting conditions. In response to forced swimming, a similar increase in plasma adrenocorticotropin and corticosterone was observed in KO and WT animals. Stressor exposure triggered also an increased epinephrine release in WT animals, but did not significantly alter plasma epinephrine levels in KO mice. These data suggest that the chronic absence of nNOS reduces the capacity of epinephrine synthesising enzymes in the adrenal gland to respond to acute stressor exposure with an adequate epinephrine release.