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Effect of chronic intermittent hypobaric hypoxia on α1-adrenergic receptor of myocardium participates in the cardioprotection

WANG Ying-Ping^1,2, CUI Fang², ZHANG Li-Ping², YANG Chang-Ying², GUAN Yue², ZHOU Zhao-Nian², ZHANG Yi^2,*

¹Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China；² Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

Abstract

The purpose of the present study was to investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on α1- adrenergic receptors and the role of α1-adrenergic receptors in the protection of CIHH against ischemic injury of myocardium. Sixtysix 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 (pB=404 mmHg, pO2=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 ºC) and perfusion speed (12 mL/min). Muscle contraction was evoked by electric stimuli. Different concentrations (1×10-7, 1×10-6 and 1×10-5 mol/L) of phenylephrine (PE), an α1-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 (1×10-6 mol/L), an α1-adrenergic receptor antagonist, was used to investigate the role of α1-adrenergic receptor in the protective effect of CIHH on papillary muscle. The results showed: (1) PE increased the maximal isometric tension (Pmax) and maximal velocity of tension development (PdT/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 1×10-5 mol/L of PE, the increases of Pmax and PdT/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 Pmax and PdT/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 (1×10-6 mol/L). The results of the present study suggest that CIHH increases the activity of α1-adrenergic receptor, which is possibly one of the mechanisms for the cardioprotection of CIHH.

Key words: chronic intermittent hypobaric hypoxia; α1-adrenergic receptor; phenylephrine; prazosin; papillary muscle; rat

Received: 2008-07-08　　Accepted: 2008-10-15

Corresponding author: 张翼　　E-mail: zhyhenry@hotmail.com

Citing This Article：

WANG Ying-Ping, CUI Fang, ZHANG Li-Ping, YANG Chang-Ying, GUAN Yue, ZHOU Zhao-Nian, ZHANG Yi. Effect of chronic intermittent hypobaric hypoxia on α1-adrenergic receptor of myocardium participates in the cardioprotection. Acta Physiol Sin 2009; 61 (1): 21-26 (in Chinese with English abstract).