Wang Ying-Ping, Cui Fang, Zhang Li-Ping, Yang Chang-Ying, Guan Yue, Zhou Zhao-Nian, Zhang Yi
Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.
Sheng Li Xue Bao. 2009 Feb 25;61(1):21-6.
The purpose of the present study was to investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on α(1)-adrenergic receptors and the role of alpha(1)-adrenergic receptors in the protection of CIHH against ischemic injury of myocardium. Sixty-six adult male Sprague-Dawley rats were randomly divided into four groups: control group (Con), 14-day CIHH treatment group (CIHH14), 28-day CIHH treatment group (CIHH28) and 42-day CIHH treatment group (CIHH42). CIHH rats were exposed to hypoxia mimicking 5 000 m altitude (p(B)=404 mmHg, p(O(2))=84 mmHg) in a hypobaric chamber, 6 h daily for 14, 28 and 42 d, respectively. Control animals lived in the same environment as CIHH animals except hypoxia exposure. After anesthesia with sodium pentobarbital (3.0-3.5 mL/kg body weight, i.p.), papillary muscle was taken from the right ventricle of rat and perfused with modified Tyrode's solution continuously, at constant temperature (37 °C) and perfusion speed (12 mL/min). Muscle contraction was evoked by electric stimuli. Different concentrations (1x10(-7), 1x10(-6) and 1x10(-5) mol/L) of phenylephrine (PE), an alpha(1)-adrenergic receptor agonist, were applied cumulatively to investigate the effect of PE on the mechanic contraction of right ventricular papillary muscles of rats in Con, CIHH14, CIHH28 and CIHH42 groups. Also, prazosin (1x10(-6) mol/L), an α(1)-adrenergic receptor antagonist, was used to investigate the role of α(1)-adrenergic receptor in the protective effect of CIHH on papillary muscle. The results showed: (1) PE increased the maximal isometric tension (P(max)) and maximal velocity of tension development (P(dT/dt)) of muscle contraction in a dose-dependent manner (P<0.05), and the increase of the muscle contraction was much greater in CIHH28 and CIHH42 rats than that in Con rats (P<0.05). Under 1x10(-5) mol/L of PE, the increases of P(max) and P(dT/dt) over the baseline were 51.2% and 44.5% in CIHH28 group, 48.6% and 44.5% in CIHH42 group, and 28.7% and 24.5% in Con group, respectively; (2) The contraction of papillary muscle decreased during simulated ischemia, but the decrease was slighter in CIHH rats than that in Con rats (P<0.05). The decreases in P(max) and P(dT/dt) were 59.6% and 53.6% in CIHH28 group, 60.4% and 49.9% in CIHH42 group, and 74.4% and 64.7% in Con group, respectively; (3) The protective effect of CIHH on ischemic papillary muscle was abolished by prazosin (1x10(-6) mol/L). The results of the present study suggest that CIHH increases the activity of α(1)-adrenergic receptor, which is possibly one of the mechanisms for the cardioprotection of CIHH.
本研究旨在探讨慢性间歇性低压低氧（CIHH）对α（1）-肾上腺素能受体的影响以及α（1）-肾上腺素能受体在CIHH保护心肌免受缺血性损伤中的作用。66只成年雄性Sprague-Dawley大鼠随机分为四组：对照组（Con）、CIHH处理14天组（CIHH14）、CIHH处理28天组（CIHH28）和CIHH处理42天组（CIHH42）。CIHH大鼠分别在低压舱中暴露于模拟海拔5000米的低氧环境（p（B）=404 mmHg，p（O₂）=84 mmHg），每天6小时，持续14、28和42天。对照动物除不暴露于低氧环境外，生活在与CIHH动物相同的环境中。用戊巴比妥钠（3.0 - 3.5 mL/kg体重，腹腔注射）麻醉后，从大鼠右心室取出乳头肌，在恒温（37℃）和灌注速度（12 mL/min）下用改良的台氏液持续灌注。通过电刺激诱发肌肉收缩。累积应用不同浓度（1×10⁻⁷、1×10⁻⁶和1×10⁻⁵ mol/L）的苯肾上腺素（PE，一种α（1）-肾上腺素能受体激动剂），以研究PE对Con、CIHH14、CIHH28和CIHH42组大鼠右心室乳头肌机械收缩的影响。此外，使用α（1）-肾上腺素能受体拮抗剂哌唑嗪（1×10⁻⁶ mol/L）来研究α（1）-肾上腺素能受体在CIHH对乳头肌保护作用中的作用。结果显示：（1）PE以剂量依赖性方式增加肌肉收缩的最大等长张力（P（max））和最大张力发展速度（P（dT/dt））（P<0.05），且CIHH28和CIHH42组大鼠肌肉收缩的增加幅度明显大于Con组大鼠（P<0.05）。在1×10⁻⁵ mol/L的PE作用下，CIHH28组P（max）和P（dT/dt）较基线的增加幅度分别为51.2%和44.5%，CIHH42组分别为48.6%和44.5%，Con组分别为28.7%和24.5%；（2）在模拟缺血期间乳头肌收缩减弱，但CIHH组大鼠的减弱程度小于Con组大鼠（P<0.05）。CIHH28组P（max）和P（dT/dt）的降低幅度分别为59.6%和53.6%，CIHH42组分别为60.4%和49.9%，Con组分别为74.4%和64.7%；（3）哌唑嗪（1×10⁻⁶ mol/L）消除了CIHH对缺血乳头肌的保护作用。本研究结果表明，CIHH增加了α（1）-肾上腺素能受体的活性，这可能是CIHH心脏保护作用的机制之一。
