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Am J Physiol Heart Circ Physiol 283: H1577-H1587, 2002. First published July 8, 2002; doi:10.1152/ajpheart.00218.2002
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Vol. 283, Issue 4, H1577-H1587, October 2002

alpha 1-Adrenoceptor stimulation directly induces growth of vascular wall in vivo

Cauveh Erami, Hua Zhang, Jason G. Ho, David M. French, and James E. Faber

Department of Cell and Molecular Physiology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7545

Previous studies suggesting that norepinephrine is directly trophic for the vascular wall have been confounded by concomitant hemodynamic disturbances. Herein, a microcatheter connected to an osmotic minipump was implanted adjacent to the rat carotid for 2-wk perivascular suffusion of agents at systemic levels ~1,000 times below the threshold for altering arterial pressure. Norepinephrine decreased lumen and adventitial areas and circumference by 10, 14, and 5%, respectively (all P < 0.05); a nonsubtype-specific alpha 1-adrenoceptor (AR) antagonist had no effect. When begun at the time of balloon injury, 2-wk norepinephrine increased lumen loss by 45%, increased neointimal area by 64% and collagen content by 33%, and reduced vessel circumference by 5% (all P < 0.05). alpha 1-AR antagonists decreased neointimal area by 33% (all P < 0.05). alpha 1A-AR antagonist reduced lumen loss by 70%, neointimal area by 54%, circumference decline by 84%, and adventitial thickening by 87% (all P < 0.05), whereas alpha 1B-, alpha 1D-, alpha 2- and beta -AR antagonists were without effect. These are the first in vivo studies demonstrating that norepinephrine is directly trophic for the vascular wall and augments injury-induced intimal lesion growth.

artery; smooth muscle; adventitia; injury; adrenergic


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