VISUALIZATION OF HIGH-AFFINITY AND LOW-AFFINITY BETA-ADRENERGIC RECEPTORS IN RAT LUNG - UP-REGULATION BY CHRONIC HYPOXIA

Chronic hypoxia induces a hyperadrenergic state which down-regulates beta-adrenergic receptors (beta-AR) in the heart. We visualized lung beta-AR binding sites after adaptation to chronic hypoxia by autoradiography of whole lung sections labeled with 50 pM I-125-labeled pindolol. A low concentration of agonist (32 nM isoproterenol) selectively masked beta-ARs with high affinity for agonists. Total specific beta-AR binding increased twofold with hypoxia. In both the control and hypoxic lung sections, 60-70% of the beta-Ars were in a high-affinity state. which could be reversed by guanine nucleotide. Autoradiography revealed a high density of high- and low-affinity beta-AR sites in lung parenchyma, predominantly involving alveolar walls, but also the walls of airways and blood vessels. The distribution of high- and low-affinity beta-AR within the lung was qualitatively identical. Hypoxia increased beta-AR binding without affecting its distribution. The majority of the additional beta-ARs induced during adaptation to chronic hypoxia are in the high-affinity state, and are thus of probable functional significance.