Influence of Carbon Monoxide, and its Interaction with Nitric Oxide, on the Adrenocorticotropin Hormone Response of the Normal Rat to a Physico‐Emotional Stress

Abstract

We determined whether the gas carbon monoxide (CO) altered the adrenocorticotropin hormone (ACTH) response to mild inescapable electrofootshocks, and whether it interacted with nitric oxide (NO). Peripheral injection of the NO synthase (NOS) inhibitor Nwnitro-L-arginine-methylester (L-NAME), a compound which readily crosses the blood-brain barrier, produced the expected blunting of the ACTH response to the shocks. This effect was mimicked by other arginine analogues such as L-nitroarginine (L-NNA) and NG-methyl-L-arginine (NMMA). The subcutaneous (s.c.) administration of the heme oxygenase (HO) blockers tin mesoporphyrin (SnMP) or tin protoporphyrin (SnPP) significantly decreased brain HO levels, indicating that both compounds had penetrated the brain. Blood pressure showed a modest increase in response to SnMP, and no change after SnPP. SnMP and SnPP both decreased shock-induced ACTH release, though the magnitude of this effect was slightly less than that of L-NAME. The influence of SnPP was further augmented in rats with concomitant blockade of NO formation, which suggests that both NO and CO are necessary for the full response of this axis to electrofootshocks. Finally, the ability of SnPP to significantly blunt the expression of the mRNA for the immediate early gene NGFI-B in the paraventricular nucleus (PVN) of rats exposed to shocks, indicates that the influence of CO was exerted on hypothalamic neuronal activity. Collectively, our results show that NO and CO exert a stimulatory effect on the HPA axis response to mild electrofootshocks, and that at least part of this influence takes place on hypothalamic neurons and/or their afferents.

CB1 receptor activation in the rat paraventricular nucleus induces bi-directional cardiovascular effects via modification of glutamatergic and GABAergic neurotransmission

“…The effectiveness of the antagonists on centrally mediated effects after their i.v. application was confirmed in our previous publications (MK801, ICI118551 and SQ29548; Malinowska et al 2010; Grzęda et al 2015) or by other investigators (L-NAME, bicuculline and losartan; Turnbull et al 1998; Elsersy et al 2006; Busnardo et al 2014). Moreover, (1) we have shown previously that central but not peripheral NMDA, β 2 and TP receptors are involved in the pressor effect of cannabinoids since the effects of AEA or MetAEA given i.v.…”

Role of Heme Oxygenase in Modulating Endothelial Function in Mesenteric Small Resistance Arteries of Spontaneously Hypertensive Rats

“…In both SHRs and WKYs, short-term treatment with SnMP induced a reduction of blood pressure. Since the drug passes the blood-brain barrier, it is possible that central mechanisms (reduction in sympathetic nervous system activity or a Adreno Cortico Tropic Hormone (ACTH) release) may be involved in the observed findings (37). The decrease in blood pressure have not influcenced our results in terms of vascular functional responses, since in our study they have been evaluated in vitro, with no actual pressure or flow.…”

Stimulation of the pituitary–adrenal axis and of adrenocortical steroidogenesis ex vivo by administration of di-2-ethylhexyl phthalate to prepubertal male rats

“…First, acute exposure (hours) to phthalates was found to induce a rapid and transient increased production of interleukin (IL)-1 by the rat testis (Granholm et al 1992), and mono phthalates were recently shown to enhance IL-6 and IL-8 syntheses in the human epithelial A 549 cell line (Jepsen et al 2004). Secondly, proinflammatory cytokines have been reported to induce release of CRF from the PVN and augment neurochemical stimulation of the pituitary gland (Turnbull et al 1998). Apart from a stress response triggered by immuneinflammatory stimuli, cytokines may be involved in mediating hypothalamic responses to different types of stress.…”