Carotid body ablation restores astrocyte/microglia morphology in the NTS and reduces hypertension following long-term intermittent hypoxia

Chronic intermittent hypoxia (CIH) heightened carotid body (CB) chemosensory discharges, which contributes to hypertension development. Previously, we reported that CB ablation significantly reduced blood pressure after 21 days of CIH; however, whether CB-mediated glial cell activation in the caudal Nucleus of the Solitary Tract (cNTS) following long-term CIH contribute to maintain high blood pressure and enhanced ventilatory chemoreflex remains unknown. To test this hypothesis, we exposed male C57BL6 mice to CIH (5% F I O 2 , 12 times/h, 8 h/day) for 60 days. At 45 days of CIH, CBs were selectively denervated, and animals returned to CIH for 15 more days. At the end of the experimental protocol, we measured arterial blood pressure, hypoxic ventilatory response (HVR) in awake mice and characterized astrocyte and microglia morphological features using Sholl analysis. CIH induces hypertension (MABP: 83.47±1.39 vs. 95.00±2.18 mmHg; Sham vs. CIH), increases the HVR (1.69±0.17 vs. 4.31±0.87 ΔV E /min; Sham vs. CIH), modify cNTS astrocytes phenotype (N° of branches: 13.01±0.66 vs. 11.31±0.52; cable length: 181.00±8.90 vs 148.10±1.48 μm, convex hull: 788.10±37.60 vs. 584.30±23.75 μm 3 ; Sham vs. CIH), and microglia arborization (N° of branches: 196.10±8.35 vs. 376.30±16.80; cable length: 667.4±29.63 vs. 1267±60.47 μm, convex hull: 6177±362 vs. 9721±564 μm 3 ; Sham vs. CIH). Importantly, CB denervation normalized the elevated blood pressure (MABP: 83.47±1.38 mmHg; CIHd), the altered peripheral chemoreflex response (HVR: 1.63±0.43 ΔV E /min; CIHd) and morphological changes in astrocytes (N °of branches: 17.23±0.88, cable length: 231.70±12.87, convex hull: 982.70±55.55 μm 3 ) and microglia located in the cNTS (N° of branches 126.20±13.34; cable length: 126.2±13.3, Convex hull size: 3584±380 μm 3 ; CIHd). Present results suggest that CBs play a crucial role in the maintenance of high arterial pressure and respiratory alterations induced by long-term CIH and may contribute to the formation of a neuroinflammatory niche at the cNTS by modifying glial cell activity. Supported by Fondecyt Grants 1211443 and 1220950. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.