Alpha(1)-adrenoceptor stimulation directly induces growth of vascular wall in vivo.
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(1)A-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.
Erami
Cauveh
C
Department of Cell and Molecular Physiology, School of Medicine, University of North Carolina, Chapel Hill 27599-7545, USA.
Zhang
Hua
H
Ho
Jason G
JG
French
David M
DM
Faber
James E
JE
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D007097:Imines / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010075:Oxathiins / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012008:Recurrence; D017539:Tunica Intima / Q000166:cytology / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
C434277:AH 11110A; D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D007097:Imines; D007211:Indoles; D010075:Oxathiins; D010879:Piperazines; D010880:Piperidines; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; C050877:benoxathian; D011433:Propranolol; C095285:silodosin; C058525:2-methoxyidazoxan; C053428:BMY 7378; D009638:Norepinephrine; D019329:Idazoxan