Department of Pharmaceutical Sciences, Feik School of Pharmacy, University of the Incarnate Word, San Antonio, TX 78209, USA.
Am J Physiol Heart Circ Physiol. 2013 Aug 1;305(3):H403-9. doi: 10.1152/ajpheart.00317.2013. Epub 2013 May 24.
Exposure to chronic intermittent hypoxia (CIH) is an animal model that mimics the repetitive bouts of hypoxemia experienced by humans with sleep apnea. Rats exposed to CIH develop hypertension that depends on the activation of sympathetic nerve activity (SNA). Since obesity and metabolic syndrome have been linked to neurogenic hypertension and sleep apnea, and because sleep apnea can adversely affect aerobic exercise capacity, we tested the hypothesis that rats bred for selection of low aerobic capacity running (LCR) would have a greater hypertensive response to CIH than rats bred for high aerobic capacity running (HCR). Blockade of ganglionic transmission was performed to compare the contribution of SNA to the maintenance of resting mean arterial pressure (MAP). Next, hypertensive responses to 7 days of CIH were compared across LCR and HCR rats (14-16 mo old). Finally, the contribution of the hypothalamic paraventricular nucleus (PVN) to the maintenance of SNA and hypertension after CIH was determined and compared across groups. Although LCR rats were less active and had greater body weights than HCR rats, resting MAP, the contribution of ongoing SNA to the maintenance of MAP, and hypertensive responses to CIH were similar between groups. Contrary to our hypothesis, chemical inhibition of the PVN with muscimol (1 mmol/100 nl) caused a larger fall of MAP in HCR rats than in LCR rats. We conclude that LCR rats do not have resting hypertension or an exaggerated hypertensive response to CIH. Interestingly, the maintenance of CIH hypertension in LCR rats compared with HCR rats appears less reliant on ongoing PVN neuronal activity.
慢性间歇性低氧(CIH)暴露是一种动物模型,可模拟患有睡眠呼吸暂停的人类反复出现的低氧血症。暴露于 CIH 的大鼠会发展为高血压,这取决于交感神经活动(SNA)的激活。由于肥胖和代谢综合征与神经性高血压和睡眠呼吸暂停有关,并且睡眠呼吸暂停会对有氧运动能力产生不利影响,因此我们测试了这样一个假设,即选择低有氧能力跑步(LCR)的大鼠对 CIH 的高血压反应会比选择高有氧能力跑步(HCR)的大鼠更大。进行了神经节传递阻断以比较 SNA 对维持静息平均动脉压(MAP)的贡献。接下来,在 LCR 和 HCR 大鼠(14-16 个月大)之间比较了对 7 天 CIH 的高血压反应。最后,确定并比较了下丘脑室旁核(PVN)在 CIH 后维持 SNA 和高血压中的作用。尽管 LCR 大鼠的活动量和体重均大于 HCR 大鼠,但静息 MAP、持续 SNA 对 MAP 的维持作用以及对 CIH 的高血压反应在两组之间相似。与我们的假设相反,用 muscimol(1 mmol/100 nl)化学抑制 PVN 导致 HCR 大鼠的 MAP 下降幅度大于 LCR 大鼠。我们的结论是,LCR 大鼠没有静息性高血压或对 CIH 的高血压反应过度。有趣的是,与 HCR 大鼠相比,LCR 大鼠维持 CIH 高血压的能力似乎较少依赖于持续的 PVN 神经元活动。