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J Am Coll Cardiol, 2009; 54:1137-1145, doi:10.1016/j.jacc.2009.05.056
© 2009 by the American College of Cardiology Foundation
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The Alpha-1D Is the Predominant Alpha-1-Adrenergic Receptor Subtype in Human Epicardial Coronary Arteries

Brian C. Jensen, MD*,{dagger}, Philip M. Swigart, MS*, Marie-Eve Laden, MD*, Teresa DeMarco, MD{dagger}, Charles Hoopes, MD{ddagger} and Paul C. Simpson, MD*,{dagger},*

* Cardiology Section, San Francisco VA Medical Center, San Francisco, California
{dagger} Division of Cardiology, University of California, San Francisco, San Francisco, California
{ddagger} Division of Cardiothoracic Surgery, University of California, San Francisco, San Francisco, California


Figure 1
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Figure 1 {alpha}1-AR Subtype mRNA Levels in Coronary Arteries and Left Ventricle

Quantitative real-time reverse transcription polymerase chain reaction of {alpha}1-adrenergic receptor (AR) subtypes in (A) human coronary arteries and (B) left ventricle free wall. mRNA = messenger ribonucleic acid; TBP = TATA-binding protein.

 

Figure 2
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Figure 2 {alpha}1- and β-AR Protein Levels by Saturation Binding

Saturation radioligand binding was done in membranes pooled from 15 epicardial coronary arteries of 11 patients. (A) Binding with 3H-prazosin for total {alpha}1-adrenergic receptors (ARs); (B) binding with 125I-CYP for total β-ARs. CYP = cyanopindol; DPM = disintegrations/minute.

 

Figure 3
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Figure 3 {alpha}1-AR Subtype Protein Levels by Competition Binding

Competition for 3H-prazosin binding by the {alpha}1D-selective antagonist BMY-7378 yielded (A) a 2-site binding curve with predominantly high-affinity sites in coronary artery membranes; (B) a 1-site low affinity curve in ventricular myocardium from 3 patients. AR = adrenergic receptor.

 

Figure 4
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Figure 4 {alpha}1-AR–Induced ERK Activation in Human Coronary Artery SMCs

Cultured human epicardial coronary smooth muscle cells (SMCs) and coronary media rings were treated for 15 to 30 min with low concentrations of norepinephrine (NE) (1 to 200 nmol/l, mean 27 nmol/l), and the nonselective β-adrenergic receptor (AR) antagonist propranolol (1 µmol/l), in the absence or presence of the {alpha}1D-selective antagonist BMY-7378 (10 nmol/l) or the nonselective {alpha}1-antagonist prazosin (1 µmol/l). (A) Western blot showing extracellular signal-regulated kinase (ERK) activation in duplicate dishes from a Lonza (Walkersville, Maryland) SMC culture; (B) summary data for 8 Lonza SMC preparations from 2 patients, a ring preparation from 1 patient, and 2 primary SMC cultures from 1 patient.

 

Figure 5
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Figure 5 {alpha}1-Subtype mRNA Levels by Clinical Variables

Quantitative real-time reverse transcription polymerase chain reaction for {alpha}1-subtype messenger ribonucleic acid (mRNA) levels and all {alpha}1 mRNA are displayed according to (A) coronary artery disease (CAD); (B) β-blocker use, all carvedilol, except metoprolol (circles) and nadolol (squares); (C) β-agonist exposure; (D) age; and (E) ejection fraction. The p values are for multivariate analysis.

 




 
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