Published Online
on August 6, 2009

A more recent version of this article appeared on November 1, 2009

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Original Article

Alpha-1-Adrenergic Receptor Subtypes in Non-Failing and Failing Human Myocardium

Brian C. Jensen¹; Philip M. Swigart²; Teresa DeMarco³; Charles Hoopes³ and Paul C. Simpson^1,4

¹ San Francisco VA Medical Center and UCSF, San Francisco, CA;
² San Francisco VA Medical Center, San Francisco, CA;
³ University of California - San Francisco, San Francisco, CA

^* Corresponding author; email: paul.simpson{at}ucsf.edu

Background—Alpha-1-adrenergic receptors (1-ARs) play adaptive roles in the heart and protect against the development of heart failure (HF). The three 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 down-regulated in heart failure.

Methods and Results—Hearts from transplant recipients and unused donors were failing (n = 12; mean EF 24%) or non-failing (n = 9; mean EF 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 PCR and radioligand binding. All three 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 were not down-regulated, in contrast with β1-ARs.

Conclusion—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 that the 1-subtypes are not down-regulated in HF. Since 1-subtypes in the human heart are similar to mouse, where adaptive and protective effects of 1-subtypes are most convincing, it might become feasible to treat HF with a drug targeting the 1A and/or 1B.

Key Words: heart failure • myocardium • receptors, adrenergic, alpha • receptors, adrenergic, beta