Abstract:
Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play important roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB dependence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of the exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter endothelial function or the contractile response to phenylephrine (PE) in these arteries. In contrast, CIH exposure increased the systemic arterial pressure and enhanced the contractile response to PE while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.
摘要:
实验证据表明,慢性间歇性缺氧(CIH),阻塞性睡眠呼吸暂停(OSA)的主要标志,提高颈动脉体(CB)反应性,从而导致交感神经活动增加,动脉和肺动脉高压,和心血管疾病。增强的循环化学反射,氧化应激,和NO信号传导似乎在啮齿动物对CIH的这些反应中起重要作用。由于豚鼠具有功能低下的CB(即,这是一个自然的CB淘汰赛),在这项研究中,我们将其用作研究CIH对肺血管反应的影响的CB依赖性模型,包括那些由NO介导的,通过将它们与先前在大鼠中描述的进行比较。我们分析了肺动脉压(PAP),缺氧性肺血管收缩(HPV)反应,体内和体外的内皮功能,和血管重塑(内膜-中膜厚度,胶原纤维含量,和血管腔面积)。我们证明了30天的豚鼠暴露于CIH(FiO2,5%持续40秒,30周期/h)诱导肺动脉重塑,但不会改变这些动脉中的内皮功能或对去氧肾上腺素(PE)的收缩反应。相比之下,CIH暴露会增加全身动脉压,并增强对PE的收缩反应,同时减少主动脉中对卡巴胆碱的内皮依赖性血管舒张,而不会引起其重塑。我们得出的结论是,由于所有这些作用都与CB敏化无关,肯定还有其他氧传感器,除了CB之外,具有改变CIH中心脏和血管功能和结构的自主神经控制的能力。