Cortocotropin releasing hormone neurons in the paraventricular nucleus of the hypothalamus co‐labeled with nNOS are activated by acute hypoxia (710.8)

Acute hypoxia (AH) increases vasopressin (AVP) and corticosteroid secretion through a peripheral chemoreceptor pathway including the PVN. Previously we found that AH activates ~ 6% of AVP and 15% of nNOS cells in the PVN, but the activated nNOS cells were neither AVP nor spinally projecting (pre‐sympathetic) (McCalmon et al, 2013). In the current study conscious rats were normoxic (N, 21% O2, n = 4) or AH (10% O2, n = 5) for 2 hrs, followed by immunohistochemical evaluation of Fos‐ , CRH‐, and nNOS‐IR. Spinally‐projecting neurons were identified by prior retrograde tracer labeling. nNOS cells in the PVN contained CRH in both N (46 ±6%) and AH rats (39 ±4%). More nNOS cells were activated in AH (nNOS + Fos; 16 ±2%) compared to N rats (5±1%) . AH did not activate spinal neurons, but resulted in greater activation of CRH neurons (15 ±2%) compared to N rats (5 ±2%). Of the activated nNOS cells in AH rats, half also co‐labeled with CRH (50 ± 5%). Nitric oxide is generally inhibitory in the PVN due to enhanced GABA release and CRH, AVP, and presympathetic neurons receive robust GABAergic innervation. Thus, activation of CRH cells which contain nNOS might serve as an early compensatory mechanism to increase NO and limit increases in CRH and downstream secretion of ACTH and corticosteroids. Since NO is highly diffusible, increased NO in the PVN may also prevent activation of spinal, and limit activation of AVP neurons during AH. Grant Funding Source : NIH R01 HL98602