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Chronic Intermittent Hypoxia and Hypertension

Obstructive sleep apnea syndrome (OSA) is a complete or partial airway obstruction that can cause significant physiological disturbances with various clinical impacts such as snoring, nocturnal awakening, or daytime sleepiness. One main characteristic found in patients with OSA is hypertension, which is often linked to the severity of disease[1]. It was reported that one key pathological mechanism involved in OSA is chronic intermittent hypoxia (CIH) which induces cardiac dysfunction[2]. Furthermore, the carotid body (CB) plays a critical role in CIH-induced hypertension,. The carotid body is a major regulator of sympathetic nerve activity and CIH increases its sensory nerve response to acute hypoxia. Studies detailed that carotid body ablation prevents this CIH-induced sympathetic nerve activation and hypertension in rodents[3]. These observations might indicate CIH-related CB activation as an underlying mechanism causing the activation of the sympathetic nervous system, leading to hypertension in OSA.

Dr. Peng’s team at the University of Chicago focused on the possible implication of Olfr78 in the CIH-induced carotid activation and the resulting sympathetic nerve response and hypertension[3]. Their focus was to better understand the mechanism of the carotid body in CIH-induced hypertension by studying an olfactory receptor (Olfr78) expressed by murine carotid bodies, and knocking out Olfr78 impaired carotid body response to acute hypoxic exposure. Moreover, they investigated a carbon dioxide catalyzer, the hemeoxygenase 2 (HO-2). Since HO-2 null mice showed spontaneous apneic episodes during sleep, they tested the carotid body sensory nerve response to hypoxia in HO-2 null mice and observe if it was also amplified as seen in CIH-treated mice.

After exposing Olfr78 null mice to CIH, Dr. Peng’s team found that CIH increases blood pressure and heart rate in wild-type (WT) but not in Olfr78 null mice. Furthermore, apneic episodes per hour were measured in WT, HO-2, and HO-2/Olfr78 double null mice using the Whole-Body Plethysmography system. These measurements helped highlight that HO-2 null mice breathing patterns were irregular (58 ± 1.2 apneas/hour) compared to HO-2/Olfr78 double null mice with a relatively stable breathing (12 ± 1.3 apneas/hour). Additionally, HO-2 null mice showed enhanced carotid body sensory response to acute hypoxia and this effect was absent in HO-2/Olfr78 double null mice. Therefore, these current results do suggest evidence for Olfr78 participation in carotid body-dependent sympathetic nerve activation and hypertension in two mice models of CIH. This data might help improve our comprehension on the complex pathological mechanisms involved in OSA.

References

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