目的: 通过细胞内记录方法研究慢性间歇性低压低氧(CIHH)对家兔窦房结肾上腺素能受体反应性的影响。方法:新西兰大白兔随机分为对照组(Con)、CIHH 14 d组(CIHH 14)、CIHH 28 d组(CIHH 28)3组。CIHH组动物置于低压氧舱,分别接受14、28 d模拟5 000米高原的低压低氧处理(6 h/d)。制备离体窦房结标本、描记窦房结自律细胞的生物电活动。通过累加给药法,观察不同浓度的β-肾上腺素能受体激动剂异丙肾上腺素(ISO) (0.01、0.1、1 μmol/L)和α1肾上腺素能受体激动剂苯肾上腺素(PE) (0.01、0.1、1 μmol/L)对家兔窦房结自律细胞动作电位的影响。结果:(1) CIHH对基础状态下窦房结细胞动作电位各参数无明显影响;(2)ISO浓度依赖性增加窦房结细胞动作电位0期最大除极速率(Vmax)、动作电位幅值(APA)、放电频率(RPF)、舒张期自动去极化速率(VDD),对其它参数无明显影响;(3)CIHH处理动物窦房结细胞对ISO的反应性降低;最大浓度ISO(1 μmol/L)下,CIHH14和CIHH28组的VDD、RPF、APA和Vmax的增加明显小于对照组(P〈0.05); (4)α1肾上腺素能受体激动剂PE(0.01、0.1、1 μmol/L) 对窦房结细胞动作电位各项参数均无影响。结论:CIHH降低家兔窦房结β肾上腺素能受体反应性,对α1肾上腺素能受体反应性无影响。
AIM: To investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on the activity of adrenergic receptor(AR) in rabbit sino-atrial node (SAN) by intracellular recording.METHODS: New Zealand rabbits were randomly divided into three groups: control group (Con), 14 d CIHH treatment group (CIHH14) and 28 d CIHH treatment group (CIHH28). The CIHH rabbits were exposed to a simulated 5 000 m (oxygen 11.1%) hypobaric hypoxia in hypoxic chamber for 14 d or 28 d (6 h/d), respectively. SAN preparation was used and the transmembrane action potential was recorded by micropipettes. Isoproterenol hydrochloride (ISO, agonist of β-AR) and phenylephrine (PE, agonist of α1-AR) at different concentrations (0.01, 0.1 and 1 μmol/L) were applied cumulatively to investigate the electrophysiological effect of the drugs on the rabbit SAN among Con, CIHH14 and CIHH28 groups, respectively. RESULTS: (1) CIHH didnt change the parameters of action potential of SAN recorded under basic condition. (2) ISO changed some parameters of AP significantly in a dose-dependent manner, including increases in the amplitude of AP (APA), maximal rate of depolarization (Vmax), the velocity of diastolic (phase 4) depolarization (VDD), and rate of pacemaker firing (RPF). (3) The response of AP to ISO in CIHH rabbits was decreased significantly compared to that in Con animals. Under 1 μmol/L of ISO, the increases in VDD, RPF, APA and Vmax in CIHH animals were smaller than those in Con animals (P〈0.05). (4) No effect of PE (0.01, 0.1 and 1 μmol/L) on the parameters of action potential was observed. CONCLUSION: CIHH decreases the reactivity of β-AR, but has no effect on α1-AR in SAN of rabbit.