LABORATORY INVESTIGATION: PDF OnlyThe influence of hypoxia on p-adrenergic receptors and their intracellular coupling in isolated adult canine myocytesHeathers, Guy P. PhD; Lee, Philip C. MD; Yamada, Kathryn A. PhD; Corr, Peter B. PhDAuthor Information Cardiovascular Division, Department of Medicine and the Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri, USA. Coronary Artery Disease: January 1990 - Volume 1 - Issue 1 - p 97-110 Buy Abstract The response of β-adrenergic receptors and their coupling to intracellular events during hypoxia was evaluated in isolated, intact adult canine ventricular myocytes. Myocytes exposed to 10 minutes of hypoxia (PO2, <15 mm Hg) at 37°C exhibited no change in β-adrenergic receptor number or affinity. Even longer intervals of hypoxia (30 and 60 minutes) did not result in any significant changes in β-adrenergic receptor number. However, after 120 minutes of hypoxia, the apparent β-adrenergic receptor number increased markedly. This increase in measured β-adrenergic receptor number was shown when more than 95% of the myocytes were irreversibly injured as assessed by light microscopy, electron microscopy, and release of intracellular enzymes. Although basal levels of cyclic AMP remained unchanged during normoxia and hypoxia, cyclic AMP levels stimulated by isoproterenol (10-5 M) were significantly decreased after 60 and 120 minutes of hypoxia. Furthermore, prolonged hypoxia produced a marked downward and rightward shift in the isoproterenol-stimulated cyclic AMP response curve. Enhanced cyclic AMP levels were produced and maintained by forskolin (10-4 M) stimulation in normoxic and hypoxic myocytes. These findings demonstrate that reversible hypoxic damage does not result in significant β-adrenergic receptor alterations, thus, precluding a significant contribution of increased β-adrenergic receptor density to arrhythmogenic mechanisms during early ischemia. Protracted periods of hypoxia increase the measurable number of β-adrenergic receptors only when the cells have undergone irreversible damage. The data demonstrate that the apparent increase in receptor number in damaged cells is also associated with uncoupling of the β-adrenergic receptor to production of cyclic AMP © Lippincott-Raven Publishers.