Pilot study of the effects of bariatric surgery and continuous positive airway pressure treatment on vascular function in obese subjects with obstructive sleep apnoea.

BACKGROUND: The mechanisms by which obesity and obstructive sleep apnoea (OSA) may contribute to endothelial dysfunction are unclear. AIMS: We sought to follow up a sample of obese subjects undergoing either bariatric surgery or continuous positive airway pressure (CPAP) therapy to treat OSA. We hypothesised improved vascular function with both therapeutic approaches, consistent with a reversible OSA effect on the circulation. METHODS: Twenty-seven obese (BMI ≥30 kg/m(2)) subjects with OSA underwent either bariatric surgery without CPAP (n = 12, median BMI 43.7 kg/m(2) IQR 9.4) or CPAP (n = 15, median BMI 33.8 kg/m(2) IQR 6.6). Polysomnography and vascular testing (flow-mediated dilation of the brachial artery measured with high-resolution ultrasound, endothelium-dependent change in skin blood flow measured with laser Doppler flowmetry, and arterial stiffness measured with applanation tonometry) took place at baseline and after 6 months. RESULTS: Both groups showed significant improvements in the apnoea-hypopnea index and overnight oxygen saturation. Endothelium-dependent microvascular reactivity was 45.6% (IQR 37.5) at baseline in the CPAP group, which increased to 69.1% (IQR 62.3) post-treatment (P < 0.05). No significant changes were observed in the surgery group, despite significant weight loss (post-surgery BMI 32.7 kg/m2 IQR 8.6 (P < 0.01); no change in BMI was observed in the CPAP group. There were no significant changes in brachial artery flow-mediated dilation in either group. CONCLUSIONS: This pilot study demonstrates that 6 months of CPAP may be sufficient to improve endothelium-dependent microvascular reactivity, while substantial surgically induced weight loss did not result in improvements. Further research should be directed towards comparative effectiveness trials using these novel surrogate outcomes, as well as hard cardiovascular outcomes.

Acute stress-induced increases in thalamic CRH mRNA are blocked by repeated stress exposure.

Corticotropin-releasing hormone (CRH) coordinates multiple aspects of the stress response. Recently, CRH mRNA has been identified in two regions of the thalamus: the posterior nuclear group (Po), and a region located at the interface of the central medial and ventral posteromedial nucleus (parvicellular part) (CM-VPMpc). Previous studies demonstrated that in both regions CRH mRNA increases following 1 h of restraint stress, suggesting involvement of thalamic CRH in processing somatosensory and visceral information related to stress. The current study was proposed to further understand the effects of repeated and acute restraint stress on levels of thalamic CRH mRNA. Adult male rats were assigned to one of four groups in a 2 (repeated stress, no repeated) x2 (acute, no acute) design. Brain sections were processed for CRH mRNA in situ hybridization. ANOVA revealed no main effects of acute or repeated stress in either thalamic region. However, significant interactions between acute and repeated stress for levels of CRH mRNA were found for both regions of the thalamus. Compared to the no stress condition, acute restraint significantly increased CRH mRNA in the Po (39%) and the CM-VPMpc (32%). Repeated restraint did not alter baseline CRH mRNA levels, but blocked the acute restraint-induced effects. Thus, while acute stress increases levels of thalamic CRH mRNA, repeated exposure to the same stressor is without effect and prevents the acute response. These findings add to data establishing a role for thalamic CRH in the stress response and suggest a mechanism that may underlie habituation to repeated stress exposure.

Effects of acute and repeated restraint stress on corticotropin-releasing hormone binding protein mRNA in rat amygdala and dorsal hippocampus.

Corticotropin-releasing hormone (CRH) mediates endocrine, behavioral, and autonomic responses to stress. In addition to binding to two receptor subtypes, CRH binds to a CRH-binding protein (CRH-BP). While CRH-BP is hypothesized to play a role in regulating levels of free CRH and modulating the stress response, the effects of stressors on brain CRH-BP are relatively unexplored. The present study determined effects of acute and repeated restraint on CRH-BP mRNA in basolateral amygdala (BLA) and dorsal hippocampus (DH), brain regions involved in fear and motivation. Using in situ hybridization, we found that a single acute period of restraint significantly increased CRH-BP mRNA in BLA by 20% but had no effect in DH. Repeated restraint had no effect on basal levels of CRH-BP mRNA in BLA or DH. Importantly, repeated restraint blocked the effects of acute restraint in the BLA. These results demonstrate differential effects of acute and repeated restraint on CRH-BP mRNA.