Department of Physiology, School of Medicine, College of Medicine & Health, University College Cork, Cork, Ireland.
Adv Exp Med Biol. 2023;1427:43-51. doi: 10.1007/978-3-031-32371-3_5.
Sleep apnea is characterized by bouts of chronic intermittent hypoxia (CIH) that elicit sympathetic hyperactivity resulting in residual hypertension. We previously demonstrated that exposure to CIH increases cardiac output and sought to determine if enhanced cardiac contractility manifests prior to hypertension.Male Wistar rats were exposed to cyclical bouts of hypoxia (FiO = 0.05 nadir; 90 s) and normoxia (FiO = 0.21; 210 s) 8 h/day for 3 days (CIH; n = 6). Control animals (n = 7) were exposed to room air. Data are presented as mean ± SD and were analyzed using unpaired Student t-tests.Three-day exposure to CIH did not elicit changes in heart rate and blood pressure (p > 0.05). However, baseline left ventricular contractility (dP/dt) was significantly increased in CIH-exposed animals compared with control (15300 ± 2002 vs. 12320 ± 2725 mmHg/s; p = 0.025), despite no difference in catecholamine concentrations. Acute β-adrenoceptor inhibition reduced contractility in CIH-exposed animals (-7604 ± 1298 vs. -4747 ± 2080 mmHg/s; p = 0.014), to levels equivalent to control, while preserving cardiovascular parameters. Sympathetic ganglion blockade (hexamethonium 25 mg/kg; i.v.) produced equivalent cardiovascular responses suggesting similar global sympathetic activity between groups. Interestingly, gene expression of the β-adrenoceptor pathway in cardiac tissue was unchanged.Our results suggest that CIH increases cardiac contractility via β-adrenoceptor dependent mechanisms prior to development of global sympathetic hyperactivity suggesting that positive cardiac inotropy contributes to the development of hypertension in CIH-exposed rats.
睡眠呼吸暂停的特征是慢性间歇性低氧（CIH）发作，引起交感神经活性亢进，导致残余高血压。我们之前的研究表明，CIH 暴露会增加心输出量，并试图确定增强的心肌收缩力是否在高血压之前表现出来。雄性 Wistar 大鼠每天暴露于周期性低氧（FiO2 = 0.05 ；90 s）和常氧（FiO2 = 0.21；210 s）8 h （CIH；n = 6）。对照动物（n = 7）暴露于室内空气。数据表示为平均值±标准差，采用未配对学生 t 检验进行分析。3 天的 CIH 暴露不会引起心率和血压的变化（p > 0.05）。然而，与对照相比，CIH 暴露动物的左心室收缩力（dP/dt）基线显著增加（15300±2002 与 12320±2725 mmHg/s；p = 0.025），尽管儿茶酚胺浓度没有差异。急性β-肾上腺素能受体抑制降低了 CIH 暴露动物的收缩力（-7604±1298 与-4747±2080 mmHg/s；p = 0.014），使其达到对照水平，同时保持心血管参数不变。交感神经节阻断（静脉注射六烃季铵 25 mg/kg）产生了类似的心血管反应，表明各组之间存在相似的全身交感神经活性。有趣的是，心肌组织中β-肾上腺素能受体途径的基因表达没有变化。我们的结果表明，CIH 通过β-肾上腺素能受体依赖机制增加心肌收缩力，然后才发展为全身交感神经活性亢进，这表明正性心肌变力作用有助于 CIH 暴露大鼠高血压的发展。
