Perim Raphael R, Amorim Mateus R, Bonagamba The Late Leni G H, Machado Benedito H
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP 14049-900, Brazil.
Exp Physiol. 2018 Apr 1;103(4):473-482. doi: 10.1113/EP086734. Epub 2018 Feb 14.
What is the central question of this study? Chronic intermittent hypoxia (CIH) and one-kidney, one-clip experimental models lead to sympathetic overactivity and hypertension. The present study explored the impact of previous exposure to CIH on one-kidney, one-clip renal hypertension; we hypothesized that CIH potentiates its development. What is the main finding and its importance? The development of one-kidney, one-clip renal hypertension was attenuated by previous exposure to CIH, and this protective effect was eliminated by carotid body denervation. These findings indicate that inputs from peripheral chemoreceptors in CIH-preconditioned rats play a role in preventing the increase in sympathetic activity and arterial pressure induced by one-kidney, one-clip renal hypertension.
Chronic intermittent hypoxia (CIH) and one-kidney, one-clip (1K, 1C) experimental models lead to sympathetic overactivity and hypertension. We hypothesized that previous exposure to CIH potentiates the development of 1K, 1C renal hypertension. Male rats were divided into the following four groups: Control-1K, 1C, maintained under normoxia followed by 1K, 1C surgery (n = 19); Control-Sham, maintained under normoxia, followed by sham surgery (n = 19); CIH-1K, 1C, exposed to CIH (10 days) and 1K, 1C surgery (n = 19); and CIH-Sham, exposed to CIH and sham surgery (n = 18). Animals were catheterized 8 days after 1K, 1C or Sham surgeries and cardiovascular and respiratory parameters recorded on the following day. Baseline mean arterial pressure was higher in Control-1K, 1C than in Control-Sham rats (P < 0.05) and was higher in CIH-1K, 1C than in CIH-Sham rats (P < 0.05). However, the increase in mean arterial pressure in CIH-1K, 1C animals was significantly blunted in comparison to Con-1K, 1C rats (P < 0.05), indicating that previous exposure to CIH attenuates the development of renal hypertension. Systemic administration of hexamethonium, a ganglionic blocker, promoted a larger hypotensive response in Con-1K, 1C compared with CIH-1K, 1C rats (P < 0.05), suggesting that sympathetic activity was attenuated in rats previously exposed to the CIH protocol. In addition, removal of the carotid bodies before 1K, 1C renal hypertension eliminated the protective effect of CIH preconditioning on the development of the 1K, 1C hypertension. We conclude that previous exposure to CIH attenuates the development of renal hypertension via a carotid body-dependent mechanism.
本研究的核心问题是什么？慢性间歇性缺氧（CIH）和单肾单夹实验模型会导致交感神经过度活跃和高血压。本研究探讨了先前暴露于CIH对单肾单夹肾性高血压的影响；我们假设CIH会增强其发展。主要发现及其重要性是什么？先前暴露于CIH可减轻单肾单夹肾性高血压的发展，并且这种保护作用通过颈动脉体去神经支配而消除。这些发现表明，CIH预处理大鼠的外周化学感受器输入在预防单肾单夹肾性高血压诱导的交感神经活动和动脉压升高方面发挥作用。
慢性间歇性缺氧（CIH）和单肾单夹（1K，1C）实验模型会导致交感神经过度活跃和高血压。我们假设先前暴露于CIH会增强1K，1C肾性高血压的发展。雄性大鼠分为以下四组：对照-1K，1C组，在常氧条件下饲养，随后进行1K，1C手术（n = 19）；对照-假手术组，在常氧条件下饲养，随后进行假手术（n = 19）；CIH-1K，1C组，暴露于CIH（10天）并进行1K，1C手术（n = 19）；以及CIH-假手术组，暴露于CIH并进行假手术（n = 18）。在1K，1C或假手术后8天对动物进行插管，并在第二天记录心血管和呼吸参数。对照-1K，1C组的基线平均动脉压高于对照-假手术组大鼠（P < 0.05），CIH-1K，1C组高于CIH-假手术组大鼠（P < 0.05）。然而，与对照-1K，1C组大鼠相比，CIH-1K，1C组动物的平均动脉压升高明显减弱（P < 0.05），表明先前暴露于CIH可减轻肾性高血压的发展。与CIH-1K，1C组大鼠相比，神经节阻滞剂六甲铵的全身给药在对照-1K，1C组中促进了更大的降压反应（P < 0.05），表明先前暴露于CIH方案的大鼠交感神经活动减弱。此外，在1K，1C肾性高血压之前切除颈动脉体消除了CIH预处理对1K，1C高血压发展的保护作用。我们得出结论，先前暴露于CIH通过颈动脉体依赖性机制减轻肾性高血压的发展。
