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 intactrat

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 hypothalami c neurons responsible for this release. Rats that were administered SIN-1 s howed significant elevations in plasma ACTH levels, a response that was vir tually abolished by antibodies against corticotropin-releasing factor (CRF) and significantly blunted by vasopressin (VP) antiserum. SIN-1 also upregu lated 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 (C RF-R-1) in the parvocellular portion of the paraventricular nucleus (PVN) o f 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 autonomi c adjustments to altered cardiovascular activity, also responded to SIN-1 w ith 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 N O stimulates the activity of PVN neurons that control the hypothalamic-pitu itary-adrenal axis. It must be noted, however, that our results do not allo w us to determine whether this effect was direct or mediated through PVN af ferents. This study should help resolve the controversy generated by the us e of isolated brain tissues to investigate the net effect of NO on hypothal amic peptide production.