| Title | The alpha-1D Is the predominant alpha-1-adrenergic receptor subtype in human epicardial coronary arteries. | | Author(s) | Jensen BC, Swigart PM, Laden ME, DeMarco T, Hoopes C, Simpson PC | | Institution | San Francisco VA Medical Center, California 94121, USA. | | Source | J Am Coll Cardiol 2009 Sep 22; 54(13):1137-45. | | MeSH | Adult
Aged
Case-Control Studies
Coronary Artery Disease
Coronary Vessels
Female
Heart Ventricles
Humans
Male
Middle Aged
Myocardium
Myocytes, Smooth Muscle
RNA, Messenger
Receptors, Adrenergic, alpha-1
Receptors, Adrenergic, beta
Young Adult
| | Abstract | OBJECTIVES: The goal was to identify alpha-1-adrenergic receptor (AR) subtypes in human coronary arteries.
BACKGROUND: The alpha1-ARs regulate human coronary blood flow. The alpha1-ARs exist as 3 molecular subtypes, alpha1A, alpha1B, and alpha1D, and the alpha1D subtype mediates coronary vasoconstriction in the mouse. However, the alpha1A is thought to be the only subtype in human coronary arteries.
METHODS: We obtained human epicardial coronary arteries and left ventricular (LV) myocardium from 19 transplant recipients and 6 unused donors (age 19 to 70 years; 68% male; 32% with coronary artery disease). We cultured coronary rings and human coronary smooth muscle cells. We assayed alpha1- and beta-AR subtype messenger ribonucleic acid (mRNA) by quantitative real-time reverse transcription polymerase chain reaction and subtype proteins by radioligand binding and extracellular signal-regulated kinase (ERK) activation.
RESULTS: The alpha1D subtype was 85% of total coronary alpha1-AR mRNA and 75% of total alpha1-AR protein, and alpha1D stimulation activated ERK. In contrast, the alpha1D was low in LV myocardium. Total coronary alpha1-AR levels were one-third of beta-ARs, which were 99% the beta2 subtype.
CONCLUSIONS: The alpha1D subtype is predominant and functional in human epicardial coronary arteries, whereas the alpha1A and alpha1B are present at very low levels. This distribution is similar to the mouse, where myocardial alpha1A- and alpha1B-ARs mediate beneficial functional responses and coronary alpha1Ds mediate vasoconstriction. Thus, alpha1D-selective antagonists might mediate coronary vasodilation, without the negative cardiac effects of nonselective alpha1-AR antagonists in current use. Furthermore, it could be possible to selectively activate beneficial myocardial alpha1A- and/or alpha1B-AR signaling without causing coronary vasoconstriction. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19761933 |
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