α1-adrenergic receptor subtypes in nonfailing and failing human myocardium

Academic Article

Abstract

  • Background-α1-adrenergic receptors (α1-ARs) play adaptive roles in the heart and protect against the development of heart failure. The 3 α1-AR subtypes, α1A, α1B, and α1D, have distinct physiological roles in mouse heart, but very little is known about α1 subtypes in human heart. Here, we test the hypothesis that the α1A and α1B 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 α1-AR subtypes in multiple regions of both ventricles by quantitative real-time reverse-transcription polymerase chain reaction and radioligand binding. All 3 α1-AR subtype mRNAs were present, and α1A mRNA was most abundant (≈65% of total α1-AR mRNA). However, only α1A and α1B binding were present, and the α1B was most abundant (60% of total). In failing hearts, α1A and α1B binding was not downregulated, in contrast with β1-ARs. Conclusions-Our data show for the first time that the α1A and α1B subtypes are both present in human myocardium, but α1D binding is not, and the α1 subtypes are not downregulated in heart failure. Because α1 subtypes in the human heart are similar to those in the mouse, where adaptive and protective effects of α1 subtypes are most convincing, it might become feasible to treat heart failure with a drug targeting the α1A and/or α1B. (© 2009 American Heart Association, Inc.
  • Authors

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    Digital Object Identifier (doi)

    Author List

  • Jensen BC; Swigart PM; De Marco T; Hoopes C; Simpson PC
  • Start Page

  • 654
  • End Page

  • 663
  • Volume

  • 2
  • Issue

  • 6