Relative Importance of Nitric Oxide and Carbon Monoxide in Regulating the Acth Response to Immune and Non-Immune Signals

Abstract

The present work investigated the effect of nitric oxide (NO) or carbon monoxide (CO) in the ACTH response to an immune signal [the intravenous injection of interleukin-1β (IL-1β)] or to a neurogenic stressor (mild intermittent inescapable footshocks). The arginine derivative Nωnitro-L-arginine methylester (L-NAME), which non-specifically inhibits NO formation induced by all constitutive forms of NO synthase (NOS), significantly augmented the effect of IL-1β, but blockade of CO formation with metalloporphyrins was without effect. On the other hand, L-NAME blunted the effect of shocks on the early phase of ACTH release, while we had reported earlier that metalloporphyrins exerted a similar effect. This effect was mimicked by blockade of neuronal (n) NOS by Nω-Propyl-L-arginine (PA), although the resulting decrease in hormone levels was less than that induced by L-NAME. These results indicate that endogenous NO, but not CO, interferes with ACTH released by a peripheral immune signal. In contrast, NO formed by nNOS enhances the ability of shocks to induce ACTH secretion.