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(Circulation. 1999;100:2336.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Subtype Specific Regulation of Human Vascular 
1-Adrenergic Receptors by Vessel Bed and Age
From the Departments of Anesthesiology (X.L.R., J.V.B., B.L.F., K.L.C., E.B.D., H.E.M., S.O.P., C.D.R., D.A.S.), Pharmacology/Cancer Biology (D.A.S.), Surgery (D.A.S.), and Biostatistics (H.E.-M.), Duke University Medical Center, Durham, NC; and Department of Anesthesiology (D.E.B., B.W., L.M.), The Johns Hopkins Medical School, Baltimore, Md.
Correspondence to Debra A. Schwinn, MD, Box 3094, DUMC, Durham, NC 27710. E-mail Schwi001{at}mc.duke.edu
Background—
1-adrenergic
receptors (1ARs) regulate blood pressure, regional
vascular resistance, and venous capacitance; the exact subtype
(1a, 1b, 1 d) mediating
these effects is unknown and varies with species studied. In order to
understand mechanisms underlying cardiovascular
responses to acute stress and chronic catecholamine
exposure (as seen with aging), we tested two hypotheses: (1) human
1AR subtype expression differs with vascular bed, and
(2) age influences human vascular 1AR subtype
expression.
Methods and Results—Five hundred vessels from 384 patients were
examined for 1AR subtype distribution at mRNA and
protein levels (RNase protection assays, ligand binding, contraction
assays). Overall vessel 1AR density is 16±2.3fmol/mg
total protein. 1aAR predominates in arteries at mRNA
(P<0.001) and protein (P<0.05) levels;
all 3 subtypes are present in veins. Furthermore,
1AR mRNA subtype expression varies with vessel bed
(1a higher in splanchnic versus central arteries,
P<0.05); competition analysis (selected
vessels) and functional assays demonstrate 1a and
1b-mediated mammary artery contraction. Overall
1AR expression doubles with age (<55 versus 
65 years)
in mammary artery (no change in saphenous vein), accompanied by
increased 1b>1a expression
(P
0.001).
Conclusions—Human vascular 1AR subtype
distribution differs from animal models, varies with vessel bed,
correlates with contraction in mammary artery, and is modulated by
aging. These findings provide potential novel targets for therapeutic
intervention in many clinical settings.
Key Words: catecholamine • stress • arteries • veins • hypertension
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