Alpha adrenergic receptor signaling in the hypothalamic paraventricular nucleus is diminished by the chronic intermittent hypoxia model of sleep apnea

Chronic intermittent hypoxia (CIH) is a model for obstructive sleep apnea. The paraventricular nucleus (PVN) of the hypothalamus has been suggested to contribute to CIH-induced exaggerated cardiorespiratory reflexes, sympathoexcitation and hypertension. This may occur, in part, via activation of the dense catecholaminergic projections to the PVN that originate in the brainstem. However, the contribution of norepinephrine (NE) and activation of its alpha-adrenergic receptors (a-ARs) in the PVN after CIH exposure is unknown. We hypothesized CIH would increase the contribution of catecholaminergic input. To test this notion, we determined the expression of a-AR subtypes, catecholamine terminal density, and synaptic properties of PVN parvocellular neurons in response to a-AR activation in male Sprague-Dawley normoxic (Norm) and CIH exposed rats. CIH decreased mRNA for a(1d) and a(2b) AR. Dopamine-beta-hydroxylase (D beta H) terminals in the PVN were similar between groups. NE and the alpha(1)-AR agonist phenylephrine (PE) increased sEPSC frequency after Norm but not CIH. Block of alpha(1)-ARs with prazosin alone did not alter sEPSCs after either Norm or CIH but did prevent agonist augmentation of sEPSC frequency following normoxia. These responses to NE were mimicked by PE during action potential block suggesting presynaptic terminal alterations in CIH. Altogether, these results demonstrate that a1-AR activation participates in neuronal responses in Norm, but are attenuated after CIH. These results may provide insight into the cardiovascular, respiratory and autonomic nervous systems alterations in obstructive sleep apnea.

Automated summary

The study investigated the effects of CIH on PVN neurons and found that a1-AR activation plays a role in neuronal responses after CIH, which are attenuated compared to normal conditions. These findings may shed light on alterations in the cardiovascular, respiratory, and autonomic nervous systems in obstructive sleep apnea.