| Objective: Chronic intermittent hypobaric hypoxia (CIHH) has been provided a clear cardiac protection against ischemia/reperfusion or hypoxia/reoxygenation injury and arrhythmia. It is well known that adrenergic receptor (AR) plays an important role in many cardiac physiological and pathophysiological activities, but whether adrenergic receptor (AR) take part in cardiac protection of chronic intermittent hypobaric hypoxia is not clear yet. The purpose of present study is to investigate the effect of CIHH on AR and the role of AR in the cardiac protection.1 Effect of intermittent hypobaric hypoxia on reactivity of papillary muscleα1 - adrenergic receptors in ratMethods: Forty-eight rats were randomly divided into four groups, control group (Con), 14 days CIHH treatment group (CIHH14), 28 days CIHH treatment group (CIHH28) and 42 days CIHH treatment group (CIHH42). CIHH rats were exposed to hypoxia in a hypobaric chamber at 5000 m altitude, 6 hours daily for 14, 28 and 42 days, respectively. Control animals lived in the same environment as CIHH animals with free access to food and water excepting hypoxia. The hearts were quickly removed and rinsed in cold modified Tyrode's solusion (4℃) gassed with 100% oxygen. Papillary muscles were taken from the right ventricles and the contraction of muscle was recorded. The preparation was perfused with modified Tyrode's solusion continuously, at constant temperature (36±0.5℃) and speed (12 ml/min) for an hour before recording. Electric stimuli (frequency 1Hz, wave length 3 ms, 2-times threshold) were applied to excite the preparation. Differerent concentrations (0.1, 1, 10μmol/L) of phenylephrine (PE), anα1-AR agonist, were applied cumulatively to investigate the effect of CIHH on the mechanic response induced by PE in right ventricular papillary muscle of rat. Also, papillary muscles were perfused with a simulated ischemic solution and the simulated ischemic solution containing prazosin (1μmol/L), anα1-AR antaganist. Contractive parameters include the maximal isometric tension (Pmax) and velocity of tension development (PdT/dt).Results: (1) PE increase the maximal isometric tension (Pmax) and velocity of tension development (PdT/dt) of contraction significantly in a dose-dependent manner (P<0.05); (2) The response of contraction on PE in CIHH rats were increased significantly compared with that in Con rats. After PE (0.1, 1, 10μmol/L) was applied, increasing of Pmax and PdT/dt were much greater in CIHH28 (51.2, 45%) and CIHH42 (48.6, 44.5%), respectively, than that in Con (28.7, 24.5%) (P<0.05); (3) CIHH antagonized inhibition of contraction of papillary muscle induced by simulated ischemia. The decrease of Pmax and PdT/dt in CIHH28(59.6,53.6%) and CIHH42 (60.4,49.9%)were less than that in Con(74.4,64.7%) (P <0.05); (4) The protective effect of CIHH on ischemic papillary muscle was abolished by Prazosin (1μmol/L).Conclusion: CIHH increases reactivity ofα1-AR, which might be one of the mechanisms for the cardioprotection of CIHH against ischemia/reperfusion injury.2 Effect of chronic intermittent hypobaric hypoxia on reactivity of sino-atrial node adrenergic receptors in rabbitMethods: Fifteen rabbits were randomly divided into three groups: control group (Con), 14 days CIHH treatment group (CIHH14) and 28days CIHH treatment group (CIHH28). Separate sinoatrial node (SAN) preparation and record the transmembrane action potentials by micropipettes. Different concentrations (0.01, 0.1 and 1μmol/L) of Isoproterenol hydrochloride (ISO), agonist ofβ-AR and phenylephrine (PE), agonist ofα1-AR, were applied cumulatively to investigate the effect of drugs on the electrophysiology in SAN of rabbit among Con, CIHH14 and CIHH28 groups, respectively.Results: (1) CIHH didn't change the parameters of action potential of SAN of rabbit; (2) ISO changed parameters of AP significantly in a dose-dependent manner, including increase of the amplitude of AP (APA), maximal rate of depolarization (Vmax), the velocity of diastolic (phase 4) depolarization (VDD), and rate of pacemaker firing (RPF), but had no influence on other parameters; (3) The response of AP on ISO in CIHH rabbits were decreased significantly compared with that in Con animals. Under 1μmol/L of ISO, VDD and RPF increased from (39.2±3.4, 38.1±5.7) mV/s and (124±9.1, 125±4.2) beat/min to (61.0±5.8, 54.5±11.2) mV/s and (161±5.9, 156±9.0) beat/min in CIHH14 and CIHH28 group, which clearly showed an lesser increasing than that in Con group (from 40.1±3.7 mV/s to 72.1±3.5 mV/s and from 132±5.9 beat/min to 186±15.3 beat/min) (P<0.01). Vmax and APA increased from (6.5±1.8, 60.8±1.0) V/s and (6.2±1.6, 61.8±4.2) mV to (6.9±1.7, 6.9±1.7) V/s and (64.5±0.6, 64.0±1.7) mV (P<0.05) in CIHH14 and CIHH28 group, which also showed an lesser increasing than that in Con group (from 6.5±1.5 V/s to 8.9±0.4 V/s and from 60.3±2.1 mV to 67.4±2.6 mV) (P<0.05); (4) There were no change in parameters of action potential after Propranolol (1μmol/L), an antagonist ofβ- AR, was added into the bath solution throughout the experiments to eliminate the contamination ofβ-AR activation before PE (0.01, 0.1, 1μmol/L) added cumulatively.Conclusion: CIHH decreases reactivity ofβ-AR, don't change the function ofα1-AR and don't influence the electrophysiology of sinoatrial node.
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