Nitric Oxide Stimulates ACTH Secretion and the Transcription of the Genes Encoding for NGFI-B, Corticotropin-Releasing Factor, Corticotropin-Releasing Factor Receptor Type 1, and Vasopressin in the Hypothalamus of the Intact Rat

Abstract

We investigated the effect of the intracerebroventricular injection of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) on the release of adrenocorticotropin hormone (ACTH) and the neuronal response of hypothalamic neurons responsible for this release. Rats that were administered SIN-1 showed significant elevations in plasma ACTH levels, a response that was virtually abolished by antibodies against corticotropinreleasing factor (CRF) and significantly blunted by vasopressin (VP) antiserum. SIN-1 also upregulated heteronuclear (hn) transcripts for CRF and VP and messenger RNA (mRNA) levels for the immediate early gene NGFI-B and for CRF receptor type 1 (CRF-R 1 ) in the parvocellular portion of the paraventricular nucleus (PVN) of the hypothalamus. Blockade of prostaglandin synthesis with ibuprofen did not alter the ACTH or the PVN response to SIN-1. The central nucleus of the amygdala and the supraoptic nucleus, regions that are involved in autonomic adjustments to altered cardiovascular activity, also responded to SIN-1 with elevated NGFI-B mRNA levels. However, the only change in mean arterial blood pressure caused by this NO donor was a transient and modest increase. To our knowledge, this is the first demonstration that in the intact rat NO stimulates the activity of PVN neurons that control the hypothalamicpituitary-adrenal axis. It must be noted, however, that our results do not allow us to determine whether this effect was direct or mediated through PVN afferents. This study should help resolve the controversy generated by the use of isolated brain tissues to investigate the net effect of NO on hypothalamic peptide production.

Prolonged Exposure to Intermittent Alcohol Vapors Blunts Hypothalamic Responsiveness to Immune and Non‐Immune Signals

“…One hypothesis that we are presently pursuing is that nitric oxide (NO), a gas now recognized for its ubiquitous actions in the CNS, may be involved. The facts that NO stimulates CRF and VP synthesis in the PVN (Lee et al, 1999) and that prolonged alcohol ingestion reportedly decreases NO production in certain brain areas (Fitzgerald et al, 1995), suggests the possibility that at least part of the inhibitory action of long-term alcohol on the HPA axis may be due to decreased NO levels in the endocrine hypothalamus.…”

Chronic Blockade of Neuronal Nitric Oxide Synthase Does Not Affect Long‐Term Control of Blood Pressure in Normal, Saline‐Drinking or Deoxycorticosterone‐Treated Rats

“…This alteration may be due to an inhibitory effect of 7NI at this dose on arginine vasopressin (AVP) release, because nNOS and AVP are localized in the supraoptic and paraventricular nuclei (Nylen et al 2001). Nitric oxide stimulates the transcription of the gene encoding for AVP in the hypothalamus of intact rats (Lee et al 1999), and the neuroendocrine response to nociceptive stimulation determines AVP release and increases the expression of nNOS (Kurose et al 2001). Moreover, the administration of 7NI reversed the elevation in AVP in cirrhotic rats (Xu et al 2000).…”

Novel role of adrenergic neurons in the brain stem in mediating the hypothalamic–pituitary axis hyperactivity caused by prenatal alcohol exposure

“…I.c.v. cannulae were inserted according to previously published methodology (Lee et al, 1999). All cannulae were placed in the right lateral ventricle with the coordinates measured from bregma (0.4 mm posterior, 1.4 mm lateral, and 3.8 mm ventral).…”

“…and only rats with correct placement were used for the statistical analysis of the data. After one week of recovery, flexible cannulae were placed in the left carotid vein to permit repeated blood draws with minimal stress (Lee et al, 1999). Rats were allowed to recover for another two days before experiments began.…”