Fletcher E C
Department of Medicine Division of Respiratory, University of Louisville School of Medicine, Ambulatory Care Building, Room A3L01, 530 South Jackson St., Louisville, KY, USA.
Respir Physiol. 2000 Feb;119(2-3):189-97. doi: 10.1016/s0034-5687(99)00114-0.
One of the major manifestations of obstructive sleep apnea (OSA) is profound and repeated (episodic) hypoxia during sleep. Acute hypoxia leads to stimulation of the peripheral chemoreceptors, which in turn directly increase sympathetic outflow. It is believed that this increase in sympathetic outflow is directly responsible, at least in part, for the acute blood pressure (BP) changes seen in OSA. It is difficult however, to study the chronic effects of repeated episodic hypoxia (EH) in humans since the chronic cardiovascular changes may take many years to manifest. For this reason, we developed a method of providing recurrent short periods of hypoxia (resembling the episodic desaturation in humans with OSA) to rats for 35 days, stimulating the chemoreceptors and the sympathetic nervous system, allowing examination of the chronic cardiovascular response to EH. The result of EH in rats is a 10-14 mmHg increase in resting (unstimulated) mean BP that lasts for several weeks after cessation of the daily EH. This BP increase is blocked by carotid body denervation, sympathetic nerve ablation, renal sympathectomy, adrenal medullectomy, and the angiotensin-1 receptor blocker losartan. Thus, it appears that adrenergic and renin-angiotensin system over-activity contribute to the early chronic elevated BP in EH and perhaps in human hypertension associated with OSA.
阻塞性睡眠呼吸暂停（OSA）的主要表现之一是睡眠期间严重且反复（发作性）的缺氧。急性缺氧会刺激外周化学感受器，进而直接增加交感神经输出。据信，这种交感神经输出的增加至少部分直接导致了OSA中出现的急性血压（BP）变化。然而，由于慢性心血管变化可能需要数年时间才能显现，因此很难在人类中研究反复发作性缺氧（EH）的慢性影响。出于这个原因，我们开发了一种方法，为大鼠提供反复的短时间缺氧（类似于患有OSA的人类的发作性去饱和），持续35天，刺激化学感受器和交感神经系统，从而能够研究对EH的慢性心血管反应。大鼠中EH的结果是静息（未受刺激）平均血压升高10 - 14 mmHg，在每日EH停止后持续数周。这种血压升高可被颈动脉体去神经支配、交感神经切除术、肾交感神经切除术、肾上腺髓质切除术以及血管紧张素-1受体阻滞剂氯沙坦阻断。因此，似乎肾上腺素能和肾素-血管紧张素系统的过度活跃促成了EH早期慢性血压升高，或许也促成了与OSA相关的人类高血压。
