Voelkel N F, Hegstrand L, Reeves J T, McMurty I F, Molinoff P B
J Appl Physiol Respir Environ Exerc Physiol. 1981 Feb;50(2):363-6. doi: 10.1152/jappl.1981.50.2.363.
Exposure to chronic hypoxia results in a lower resting heart rate and a blunted cardiovascular responsiveness to beta-adrenergic receptor stimulation. Possible effects of acclimatization to high altitude on the binding of [125I]iodohydroxybenzylpindolol to beta-adrenergic receptors on membranes of right and left ventricles of rat heart were determined. Chronic high-altitude exposure led to a decrease in the density of beta-adrenergic receptors in nonhypertrophied left ventricles as well as in hypertrophied right ventricles. The affinity of the receptor for the radioligand was not changed by the exposure to high altitude, suggesting that the properties of the receptor were not affected. Basal and isoproterenol-stimulated adenylate cyclase activities were decreased in membranes prepared from hearts and pulmonary arteries of rats acclimatized to high altitude. The loss of cardiac beta-adrenergic receptors in rats adapted to high altitude was prevented by the chronic coadministration of a low dose of DL-propranolol. The results suggest that changes in beta-adrenergic receptor density may partially explain the hemodynamic adaptation that occurs with chronic hypoxia. These decreases may be due to a loss of functional beta-adrenergic receptors caused by chronically elevated concentrations of circulating neurally released catecholamines.
长期暴露于低氧环境会导致静息心率降低，以及心血管系统对β-肾上腺素能受体刺激的反应性减弱。我们研究了高原习服对大鼠心脏左右心室膜上[125I]碘羟基苄基吲哚洛尔与β-肾上腺素能受体结合的可能影响。长期高原暴露导致非肥厚性左心室以及肥厚性右心室中β-肾上腺素能受体密度降低。受体对放射性配体的亲和力并未因高原暴露而改变，这表明受体的性质未受影响。在适应高原环境的大鼠心脏和肺动脉制备的膜中，基础和异丙肾上腺素刺激的腺苷酸环化酶活性均降低。长期联合给予低剂量的DL-普萘洛尔可防止适应高原环境的大鼠心脏β-肾上腺素能受体的丢失。结果表明，β-肾上腺素能受体密度的变化可能部分解释了慢性低氧时发生的血流动力学适应。这些降低可能是由于循环中神经释放的儿茶酚胺浓度长期升高导致功能性β-肾上腺素能受体丢失所致。
