Sensory plasticity of carotid body is correlated with oxidative stress in paraventricular nucleus during chronic intermittent hypoxia.

Chronic intermittent hypoxia (CIH) is known to induce hypertension, but the mechanism is not well understood. We hypothesized that sensory plasticity of the carotid body (CB) and oxidative stress in the paraventricular nucleus (PVN) are involved in CIH-induced hypertension. In this study, rats were exposed to CIH for 28 days (intermittent hypoxia of 21% O2 for 60 s and 5% O2 for 30 s, cyclically repeated for 8 hr/day) and then randomly grouped for intracerebroventricular injection of 5-HT2 receptor antagonist ritanserin, Rho-associated protein kinase (ROCK) inhibitor Y-27632, and NADPH oxidase (NOX) inhibitor diphenyleneiodonium (DPI), respectively. We found that CIH increased blood pressure (BP), elevated carotid sinus nerve (CSN) and renal sympathetic nerve (RSN) activities, oxidative stress, and cell apoptosis in PVN. NOX-derived reactive oxygen species (ROS) production and cell apoptosis decreased when CIH-induced activation of 5-HT/5-HT2AR/PKC signaling was inhibited by ritanserin. In addition, RhoA expression was downregulated when oxidative stress was attenuated by DPI, while Y-27632 decreased the expression of endothelin-1, which is overexpressed in the vascular wall during hypertension. Moreover, treatment with ritanserin, DPI or Y-27632 attenuated the sensory plasticity and sympathetic hyperactivity as well as CIH-induced elevation of BP. In conclusion, CIH-induced activation of 5-HT/5-HT2AR/PKC signaling contributes to NOX-derived oxidative stress in PVN, which may cause sensory plasticity of CB, RSN hyperactivity, and elevated BP.

Establishment of a Rabbit Model of Chronic Obstructive Sleep Apnea and Application in Cardiovascular Consequences.

BACKGROUND: Although obstructive sleep apnea (OSA) has been recognized as a major risk factor for cardiovascular complications and its clinical features are well characterized, it is difficult to replicate the OSA hypoxic model in humans. We aimed to establish an experimental rabbit model for chronic OSA and to explore its application to measure blood pressure (BP), myocardial systolic function, and oxidative stress. METHODS: The rabbit model for OSA was established by repeatedly closing the airway and then reopening it. A tube specially designed with a bag that could be alternately inflated and deflated according to a predetermined time schedule, resulting in recurrent airway occlusions and chronic intermittent hypoxia (CIH) imitating OSA patterns in humans, was used. Twenty-four rabbits were randomly divided into obstruction, sham, and control groups, and their upper airways were alternately closed for 15 s and then reopened for 105 s in a 120-s-long cycle, for 8 h each day over 12 consecutive weeks. Before and after the experiment, the BP of each rabbit was monitored. Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum, superoxide dismutase (SOD) activity, malondialdehyde (MDA) and reactive oxygen species (ROS) contents, as well as Na+-K+-ATPase/Ca2+-ATPase activities in cardiac muscle were examined. In addition, cardiac functional parameters were measured using echocardiography. RESULTS: After 3 months, all rabbits in the obstruction group manifested sleepiness performance similar to that observed in OSA patients. Traces of airflow and SpO2showed that this model mimicked the respiratory events involved in OSA, including increased respiratory effort and decreased oxygen saturation. Gradually, the BP rose each month. CIH led to obvious oxidative stress and injured myocardial systolic performance. The serum levels of IL-6 and TNF-α increased significantly (64.75 ± 9.05 pg/ml vs. 147.00 ± 19.24 pg/ml and 59.38 ± 8.21 pg/ml vs. 264.75 ± 25.54 pg/ml, respectively, both P < 0.001). Compared with the sham and the control groups, myocardial activities of Na+-K+-ATPase/Ca2+-ATPase and SOD in the obstruction group decreased markedly, while ROS and MDA content increased. CONCLUSIONS: These results show that the rabbit model for OSA simulates the pathophysiological characteristics of OSA in humans, which implies that this animal model is feasible and useful to study the mechanisms involved in the cardiovascular consequences of OSA.

[Impacts of acupuncture at twelve meridians acupoints on brain waves of patients with general anxiety disorder].

OBJECTIVE: To observe the clinical efficacy of acupuncture at twelve meridians acupoints on general anxiety disorder and explore its mechanism. METHODS: Eighty patients were randomized into an acupuncture group and a clonazepam group, 40 cases in each one. In the acupuncture group, acupuncture at twelve meridians acupoints was applied, meaning quick needling at the specific acupoints of each meridian, such as Lieque (LU 7) of the Lung Meridian, Hegu (LI 4) of the Large Intestine Meridian and Shenmen (HT 7) of the Heart Meridian. After arrival of qi, the reinforcing or reducing technique was applied accordingly and the needles were not retained. In the clonazepam group, clonazepam was prescribed for oral administration. The course of treatment was 6 weeks. Before treatment and in 2, 4 and 6 weeks of treatment, respectively, Hamilton Anxiety Scale (HAMA) was evaluated in two groups and the changes in the basic electrical activity of brain waves before and after treatment were observed. RESULTS: HAMA score was reduced apparently after treatment as compared with that before treatment in two groups (all P < 0.01). The improvements of the total HAMA scores in 2, 4 and 6 weeks of treatment in the acupuncture group were superior obviously to those in the clonazepam group (all P < 0.05). After treatment, the activity of brain waves was improved remarkably, manifested as reducing of wave a frequency, increasing of wave alpha rhythm and reducing of wave theta (all P < 0.05). The efficacy was similar in comparison between the two groups (all P > 0.05). CONCLUSION: Acupuncture at the twelve meridians acupoints achieves the superior and quick effect on general anxiety disorder as compared with clonazepam and the efficacy mechanism is related to the improvements of brain waves in the patients.