Abstract 4146116: Carotid body ablation reduces hypertension following long-term intermittent hypoxia by regulating brainstem glial cell activation

Introduction: Sleep apnea is an independent risk factor for hypertension. Chronic intermittent hypoxia (CIH), a key feature of sleep apnea, is considered the main factor for the development of hypertension, which is attributed to sympathoexcitation. However, novel evidence shows that CIH enhanced CB chemosensory discharges triggering an increase in sympathetic outflow through neuronal activation in the nucleus of the solitary tract (NTS). This idea is supported by the fact that CB ablation abolish the hypertension and NTS neuroinflammation after 21 days of CIH even in the presence of CIH. However, whether CB mediate glial cell activation (well-known sentinels involved in brain inflammation) following long-term CIH remains unknown. Hypothesis: Accordingly, we propose that the maintenance of hypertension and glia cell activation within the NTS of mice exposed to long-term CIH, depends on the CB afferent discharge. Methods: We exposed male C57BL6 mice to CIH (5% FiO2, 12 times/h, 8 h/day) for 60 days. At 45 days of CIH, CBs were selectively denervated, and animals were kept in CIH for additional 15 days. At the end of the experiments, we measured arterial blood pressure (MABP), hypoxic ventilatory response (HVR) in awake mice and assessed astrocyte and microglia activity through morphological 3D reconstructions, and IL-1β, IL-6, and TNF-α gene expression in the NTS with real-time PCR. Results: CIH induces hypertension (MABP 83.5±1.4 vs. 95.0±2.2 mmHg; Sham vs CIH), enhances HVR (1.69±0.2 vs 4.3±0.9 VE/min; Sham vs. CIH), and change astrocytes morphology (N° of branches 13.0±0.7 vs 11.3±0.5; cable length 181.0±8.9 vs 148.1±1.5 pm, Sham vs CIH), and microglia arborization (N° of branches 196.1±8.4 vs 376.3±16.8; cable length 667.4±29.6 vs 1267±60.5 pm, Sham vs CIH). Remarkably, CB denervation (CIHd) normalized the hypertension (MABP 83.5±1.4 mmHg; CIHd), the enhanced HVR (1.63±0.43 VE/min; CIHd), reduced the increased IL-6 (1.2± 0.2 vs 0.4 ± 0.1, CIH vs CIHd), TNF-α (2.0±0.2 vs 1.1±0.2, CIH vs CIHd) but not IL-1β levels (3.0±0.4 CIH vs 2.6±0.5, CIH vs CIHd), and the changes observed in astrocytes (N° of branches 17.2±0.9, cable length 231.0±12.9) and microglia (N° of branches 126.2±13.3; cable length 126.2±1.3 CIHd). Conclusions: Present results suggest that CBs plays a critical role in the maintenance of high blood pressure and contribute to the inflammation in the NTS of mice exposed to long-term CIH. Supported by Fondecyt Grants 1211443 and 1220950.