Olfactory Receptor78 Participates in Carotid Body-Dependent Sympathetic Activation and Hypertension in Murine Models of Obstructive Sleep Apnea.

Olfactory receptor (Olfr) 78 participates in carotid body (CB) activation by acute hypoxia. We examined the role of Olfr78 in CB-dependent sympathetic activation and hypertension in: 1) mice treated with chronic intermittent hypoxia (CIH) patterned after blood O profiles during obstructive sleep apnea (OSA) and 2) heme oxygenase-2 (HO-2) null mice, which exhibit OSA. CIH treated wild type (WT) mice showed: enhanced CB sensory nerve response to hypoxia and sensory long-term facilitation (sLTF), hypertension, activation of the sympathetic nervous system as evidenced by spectral analysis of inter-beat interval as well as elevated plasma nor-epinephrine (NE) levels. All these responses were absent in Olfr78 null mice. HO-2 null mice showed spontaneous apneas with an apnea index (AI) of 58±1.2 apneas/hour compared to AI of 8±0.8 apneas/hour in WT mice. CBs of HO-2 null mice showed enhanced CB response to hypoxia and sLTF as well as elevated plasma NE levels and hypertension. The magnitude of hypertension correlated to AI in HO-2 null mice (P<0.01). In striking contrast, HO-2/Olfr78 double null mice showed stable breathing with an AI of 12±1.3 apneas/hour. HO-2/Olfr78 double null mice showed absence of augmented CB response to hypoxia, sLTF, elevated plasma NE levels and hypertension. These results demonstrate that Olfr78 participates in CB activation and ensuing sympathetic nerve excitation and hypertension in two mouse models of OSA.