Published online before print August 6, 2009, doi: 10.1161/CIRCHEARTFAILURE.108.846212
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Original Articles |
1-Adrenergic Receptor Subtypes in Nonfailing and Failing Human Myocardium
From the Cardiology Section and Research Service (B.C.J., P.M.S., P.C.S.), San Francisco VA Medical Center, San Francisco, Calif; Cardiology Division (B.C.J., T.D., P.C.S.), University of California, San Francisco, Calif; Cardiovascular Research Institute (P.C.S.), University of California, San Francisco, Calif; and Division of Cardiothoracic Surgery (C.H.), University of California, San Francisco, Calif.
Correspondence to Paul C. Simpson, MD, VA Medical Center (111-C-8), 4150 Clement St, San Francisco, CA 94121. E-mail paul.simpson{at}ucsf.edu
Received December 30, 2008; accepted July 22, 2009.
Background— 
1-adrenergic receptors (1-ARs) play adaptive roles in the heart and protect against the development of heart failure. The 3 1-AR subtypes, 1A, 1B, and 1D, have distinct physiological roles in mouse heart, but very little is known about 1 subtypes in human heart. Here, we test the hypothesis that the 1A and 1B subtypes are present in human myocardium, similar to the mouse, and are not downregulated in heart failure.
Methods and Results— Hearts from transplant recipients and unused donors were failing (n=12; mean ejection fraction, 24%) or nonfailing (n=9; mean ejection fraction, 59%) and similar in age (
44 years) and sex (70% male). We measured the 1-AR subtypes in multiple regions of both ventricles by quantitative real-time reverse-transcription polymerase chain reaction and radioligand binding. All 3 1-AR subtype mRNAs were present, and 1A mRNA was most abundant (65% of total 1-AR mRNA). However, only 1A and 1B binding were present, and the 1B was most abundant (60% of total). In failing hearts, 1A and 1B binding was not downregulated, in contrast with β1-ARs.
Conclusions— Our data show for the first time that the 1A and 1B subtypes are both present in human myocardium, but 1D binding is not, and the 1 subtypes are not downregulated in heart failure. Because 1 subtypes in the human heart are similar to those in the mouse, where adaptive and protective effects of 1 subtypes are most convincing, it might become feasible to treat heart failure with a drug targeting the 1A and/or 1B.
Key Words: receptors, adrenergic, alpha • receptors, adrenergic, beta • heart failure • myocardium