Enhanced Carotid Body Chemosensory Discharge is Essential for the Hypertension Induced by Chronic Intermittent Hypoxia

Abstract

Chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea, enhances carotid body (CB) discharges, leading to sympathetic overflow and hypertension. CIH produces oxidative stress (ROS) in the CB, which contributes to enhance the CB drive to the brainstem and hypothalamic nuclei related to the cardiorespiratory control, such as the nucleus of the tractus solitary (NTS), the rostral ventrolateral medulla (RVLM) and the paraventricular nucleus (PVN). We hypothesized whether the enhanced CB chemosensory drive may increase ROS levels in central cardiovascular nuclei during CIH‐induced hypertension. Accordingly, we studied the effects of CB ablation on ROS formation in the NTS, PVN and RVLM of hypertensive CIH‐rats. Male Sprague‐Dawley rats (200 g) were exposed to CIH (5–6% inspired O2 for 20s, followed by room air for 280s, 12 times/h, 8 h/day), for 28 days. Arterial blood pressure (BP) was measured by radio‐telemetry (DSI, USA). Following 21 days of CIH exposure, rats were anesthetized with isofluorane in 2% O2, and the CBs were cryogenically destroyed bilaterally using a fine‐tipped forcep cooled in liquid N2. Then, rats were maintained in CIH conditions for one more week. Another group of rats were maintained in CIH or Sham conditions for 28 days. At the end of the experiments, all animals were euthanized (pentobarbital 120mg/kg i.p.) and brains were removed and frozen at −20°C. Coronal sections of the NTS, RVLM and PVN were cut and incubated for 30 min in the dark with the ROS sensitive fluorescent probe dihydroethidium (DHE 10μM, Invitrogen USA). DHE fluorescence was measured using epifluorescence microscopy (Olympus Optical, Japan) at an excitation wavelength of 543 nm. Data were analyzed by one‐way ANOVA followed by Bonferroni's test. Compared to Sham rats, CIH‐rats showed a significant increase in mean BP (□ 10 mmHg, p<0.05). The CIH‐induced hypertension was abolished by the ablation of the CBs (CBA). ROS formation was markedly reduced by CBA in the NTS, RVLM and PVN of CIH‐exposed rats (CIH vs. CIH‐CBA: NTS: 6.2±1.5 vs. 1.5±02 au, RVLM: 4.9± 1.5 vs. 2.1±1.6 au, PVN: 5.4±1.8 vs. 1.6±05 au, p <0.05, n= 5–6 rats). Results support the evidence for an essential role of the CBs in the development and maintenance of the CIH‐induced hypertension and oxidative stress present in the NTS, RVLM and PVNSupport or Funding InformationFONDECYT 1150040This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.