ah-11110a and benoxathian

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.

Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Angioplasty, Balloon; Animals; Carotid Artery Injuries; Cell Division; Idazoxan; Imines; Indoles; Male; Muscle, Smooth, Vascular; Norepinephrine; Oxathiins; Piperazines; Piperidines; Propranolol; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1; Recurrence; Tunica Intima; Vasoconstrictor Agents