Chronic hypoxia increases beta 1-adrenergic receptor mRNA and density but not signaling in neonatal rat cardiac myocytes

Circulation
H T LiJ S Karliner

Abstract

It is well recognized that the beta-adrenergic receptor-adenylylcyclase system is altered during myocardial ischemia/hypoxia. However, there are no data regarding either regulation of beta-adrenergic receptors, particularly at the mRNA level, or adenylylcyclase activity in isolated cardiac myocytes exposed to chronic hypoxia. In a chronic hypoxia model in which neonatal rat ventricular myocytes were exposed to a 1% O2 environment for 72 hours, we investigated (1) beta 1-mRNA and receptor expression and adenylylcyclase activity and (2) beta 1-mRNA and receptor downregulation and adenylylcyclase desensitization induced by prolonged norepinephrine incubation. We found that hypoxia for 72 hours increased myocardial membrane beta 1-adrenergic receptor density by 44%. This increase was not associated with a corresponding decrease in cytosolic beta 1-adrenergic receptors. RNase protection assays demonstrated that hypoxia increased the steady-state levels of beta 1-mRNA by 109%. Adenylylcyclase activity stimulated by isoproterenol, sodium fluoride, guanyl-5'-imidodiphosphate, and forskolin in hypoxic membranes was not altered compared with normoxic controls. Hypoxia for 72 hours also did not affect norepinephrine-induced beta 1-mRNA an...Continue Reading

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Citations

Sep 29, 1999·Pharmacology & Therapeutics·L Piacentini, J S Karliner
Jan 1, 1998·Trends in Cardiovascular Medicine·J F Schmedtje, Y S Ji
Feb 22, 2001·Journal of Molecular and Cellular Cardiology·C MoriscoJ Sadoshima
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Jun 12, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Shelby L SteeleSteve F Perry
Jan 26, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Yue GuanYi Zhang
May 17, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Soochan BaeLubo Zhang

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