Fletcher E C, Bao G, Li R
Department of Medicine, Division of Respiratory, Environmental and Critical Care Medicine, Louisville Veterans Affairs Medical Center and the University of Louisville School of Medicine, Louisville, KY, USA.
Hypertension. 1999 Aug;34(2):309-14. doi: 10.1161/01.hyp.34.2.309.
Previous studies in several strains of rats have demonstrated that 35 days of recurrent episodic hypoxia (EH) (7 hours per day), with a fractional concentration of inspired oxygen that produces desaturation equivalent to the recurrent hypoxemia of sleep apnea, results in an 8 to 13 mm Hg persistent increase in diurnal systemic blood pressure (BP). Carotid chemoreceptors and the sympathetic nervous system have been shown to be necessary for development of this BP increase. Both renal artery denervation and adrenal demedullation block the BP response to chronic EH. The present study was undertaken to define further the role of the kidneys and the renin-angiotensin system in this BP increase. Separate groups of male Sprague-Dawley rats had either (1) bilateral renal artery denervation with EH, (2) sham surgery with EH, (3) sham surgery with sham EH (compressed air), (4) EH with losartan, (5) unhandled with losartan, or (6) unhandled. The experimental period lasted 35 days. Both renal-artery denervated and losartan-treated animals showed no BP change or a lowering of BP in response to EH, whereas the sham-operated EH animals showed a progressive, sustained increase in resting room air BP. BP remained at basal levels or fell in unhandled and unhandled losartan-treated animals. Plasma renin activity was elevated 4-fold versus basal levels in EH animals with renal nerves intact but remained at baseline levels in denervated animals. At the end of the experiment, renal tissue catecholamines confirmed renal denervation in those animals. In conclusion, EH causes a progressive increase in BP, mediated in part through renal sympathetic nerve activity that acts to increase renin-angiotensin system activity through angiotensin II type 1 receptors.
先前在几种大鼠品系中的研究表明，35天的反复间歇性低氧（EH）（每天7小时），吸入氧分数产生的血氧饱和度降低程度与睡眠呼吸暂停的反复低氧血症相当，会导致日间全身血压（BP）持续升高8至13毫米汞柱。颈动脉化学感受器和交感神经系统已被证明是这种血压升高发展所必需的。肾动脉去神经支配和肾上腺髓质切除术均能阻断对慢性EH的血压反应。本研究旨在进一步明确肾脏和肾素-血管紧张素系统在这种血压升高中的作用。将雄性Sprague-Dawley大鼠分为不同组，分别进行以下处理：（1）双侧肾动脉去神经支配并给予EH；（2）假手术并给予EH；（3）假手术并给予假EH（压缩空气）；（4）给予EH并使用氯沙坦；（5）未处理并使用氯沙坦；或（6）未处理。实验期持续35天。肾动脉去神经支配和氯沙坦治疗的动物对EH均未出现血压变化或血压降低，而假手术的EH动物在静息室内空气中血压则出现渐进性、持续性升高。未处理和未处理且使用氯沙坦的动物血压维持在基础水平或下降。在肾神经完整的EH动物中，血浆肾素活性相对于基础水平升高了4倍，但在去神经支配的动物中仍保持在基线水平。实验结束时，肾组织儿茶胺证实了这些动物的肾去神经支配情况。总之，EH导致血压渐进性升高，部分是通过肾交感神经活动介导的，肾交感神经活动通过1型血管紧张素受体作用于肾素-血管紧张素系统，使其活性增加。
