Chronic Hypoxia Differentially Regulates α1-Adrenergic Receptor Subtype mRNAs and Inhibits α1-Adrenergic Receptor–Stimulated Cardiac Hypertrophy and Signaling

Background After myocardial ischemia and/or infarction, surviving cardiac myocytes in and around the injured zone develop hypertrophy to compensate for the loss of contractile units due to myocyte injury and death. One of the factors that may be involved in the development of hypertrophy after ischemic injury is norepinephrine (NE), an agent that induces hypertrophy of cardiac myocytes through the α1-adrenergic receptor (AR). It is not known, however, whether hypoxia, a major component of ischemia, has any direct effect on NE-stimulated hypertrophy. Therefore, we sought to determine whether chronic hypoxia could alter NE-stimulated hypertrophy and if so, whether this alteration was related to α1-AR–mediated signaling and α1-AR changes at both the protein and mRNA levels. Methods and Results We developed a model of chronic hypoxia in cultured neonatal rat cardiac myocytes in which myocytes were exposed to 1% oxygen for 72 hours. Initially, we observed that chronic hypoxia inhibited NE-stimulated hypertroph...

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