{alpha}1-Adrenergic receptor subtypes in nonfailing and failing human myocardium.
BACKGROUND
alpha1-adrenergic receptors (alpha1-ARs) play adaptive roles in the heart and protect against the development of heart failure. The 3 alpha1-AR subtypes, alpha1A, alpha1B, and alpha1D, have distinct physiological roles in mouse heart, but very little is known about alpha1 subtypes in human heart. Here, we test the hypothesis that the alpha1A and alpha1B subtypes are present in human myocardium, similar to the mouse, and are not downregulated in heart failure.


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 ( approximately 44 years) and sex ( approximately 70% male). We measured the alpha1-AR subtypes in multiple regions of both ventricles by quantitative real-time reverse-transcription polymerase chain reaction and radioligand binding. All 3 alpha1-AR subtype mRNAs were present, and alpha1A mRNA was most abundant ( approximately 65% of total alpha1-AR mRNA). However, only alpha1A and alpha1B binding were present, and the alpha1B was most abundant (60% of total). In failing hearts, alpha1A and alpha1B binding was not downregulated, in contrast with beta1-ARs.


CONCLUSIONS
Our data show for the first time that the alpha1A and alpha1B subtypes are both present in human myocardium, but alpha1D binding is not, and the alpha1 subtypes are not downregulated in heart failure. Because alpha1 subtypes in the human heart are similar to those in the mouse, where adaptive and protective effects of alpha1 subtypes are most convincing, it might become feasible to treat heart failure with a drug targeting the alpha1A and/or alpha1B.
Jensen
Brian C
BC
Cardiology Section and Research Service, San Francisco VA Medical Center, San Francisco, Calif, USA.
Swigart
Philip M
PM
De Marco
Teresa
T
Hoopes
Charles
C
Simpson
Paul C
PC
D000328:Adult; D000368:Aged; D005260:Female; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013318:Stroke Volume; D016277:Ventricular Function, Left; D055815:Young Adult
C547713:ADRA1A protein, human; C547716:ADRA1B protein, human; C547719:ADRA1D protein, human; C547714:Adra1a protein, mouse; C547717:Adra1b protein, mouse; C547720:Adra1d protein, mouse; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1