title: Adrenergic catecholamine trophic activity contributes to flow-mediated arterial remodeling.
abstract: Stimulation of alpha1-adrenoceptors (ARs) induces proliferation, hypertrophy, and migration of vascular smooth muscle cells and adventitial fibroblasts in cell and organ culture. In vivo studies have confirmed this direct trophic action and found that endogenous catecholamines contribute to neointimal formation and wall hypertrophy induced by mechanical injury. In murine carotid artery, these effects are mediated by alpha 1B-ARs, whereas alpha 1D-ARs mediate contraction and alpha 1A-ARs are not expressed. Herein, we examined whether catecholamines also contribute to arterial wall growth in a noninjury model, i.e., flow-mediated remodeling. In wild-type mice or mice deficient in norepinephrine and epinephrine synthesis [dopamine beta-hydroxylase knockout (DBH-KO)], all distal branches of the left carotid artery (LC) except the thyroid artery were ligated to reduce flow in the LC and increase flow in the right carotid artery (RC). Twenty-one days later, negative hypertrophic remodeling of the LC [i.e., -20% (decrease) in lumen area, -2% in circumference of the external elastic lamina (CEEL), +98% (increase) in thickness of the intima media, and +71% in thickness for adventitia; P < 0.01 vs. sham ligation] and positive eutrophic remodeling of the RC [+23% in lumen area, +11% in CEEL; P < 0.01 vs. sham ligation] were inhibited in DBH-KO mice [LC: +10% intima media and +3% adventitia; RC: +9% lumen area and +3% CEEL]. This inhibition was associated with reduced proliferation in the RC and reduced apoptosis and leukocyte accumulation in the RC and LC when examined 5 days after ligation. Carotid remodeling in alpha 1D-AR-knockout mice evidenced little or no inhibition, which suggests dependence on alpha 1B-ARs. These findings suggest that catecholamine-induced trophic activity contributes to both flow-mediated negative remodeling and adaptive positive arterial remodeling.
authors.affiliation: Department of Cell and Molecular Physiology, 474 MSRB, Univ. of North Carolina, Chapel Hill, NC 27599-7545, USA.
authors.forename: Cauveh
authors.initials: C
authors.lastname: Erami
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Steven A
authors.initials: SA
authors.lastname: Thomas
authors.forename: James E
authors.initials: JE
authors.lastname: Faber
mesh_terms: D000818:Animals; D017209:Apoptosis; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency; D004837:Epinephrine / Q000172:deficiency / Q000378:metabolism*; D006984:Hypertrophy; D066298:In Vitro Techniques; D007962:Leukocytes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000172:deficiency / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000172:deficiency / Q000378:metabolism*; D012039:Regional Blood Flow
chemical_list: C547720:Adra1d protein, mouse; D018340:Receptors, Adrenergic, alpha-1; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine; D004837:Epinephrine