Published online before print September 13, 2001, doi: 10.1161/hh2101.098379
© 2001 American Heart Association, Inc.
Integrative Physiology |
Trophic Effect of Norepinephrine on Arterial Intima-Media and Adventitia Is Augmented by Injury and Mediated by Different 
1-Adrenoceptor Subtypes
From the Department of Cell and Molecular Physiology, School of Medicine, University of North Carolina, Chapel Hill, NC.
Correspondence to James E. Faber, PhD, Department of Cell and Molecular Physiology, 474 MSRB, University of North Carolina, Chapel Hill, NC 27599-7545. E-mail jefaber{at}med.unc.edu
In vivo studies have suggested that norepinephrine (NE) directly contributes to normal vascular wall growth and worsening of hypertrophy, atherosclerosis, and restenosis. However, it is unknown whether these effects are secondary to hemodynamic changes caused by systemic NE or 
-adrenoceptor (AR) antagonists. Herein, we determined if NE directly stimulates growth of medial smooth muscle cells (SMCs) and adventitial fibroblasts (AFBs) that we have shown express 1-ARs in similar abundance. The rat aorta was isolated before injury, 4 days after, or 12 days after balloon injury, and maintained under circumferential tension in organ culture for 48 hours with 1 µmol/L NE. Intima-media and adventitia were separated and DNA content, protein synthesis, and protein content measured. In uninjured aorta, NE increased DNA and protein content similarly in adventitia, and increased only protein content in intima-media, suggesting AFB proliferation and SMC hypertrophy. In vessels isolated 4 or 12 days after injury, NE increased all 3 endpoints in both layers by up to 20-fold greater than in uninjured vessels. These effects were dose-dependent and were unaffected by 2- or ß-AR blockade (except increased DNA content in adventitia that was also inhibited by 2-AR blockade). Intima-media growth was blocked by KMD3213 (1A-AR antagonist) and adventitial growth by AH11110A (1B-AR antagonist), whereas BMY7378 (1D-AR antagonist) had no effect. NE decreased SMC marker proteins (eg, -smooth muscle actin and desmin) and augmented the changes induced by injury. These data suggest that prolonged stimulation of 1A- and 1B-ARs induces growth of SMCs and AFBs, respectively, that is significantly augmented by injury.
Key Words: artery • smooth muscle cell • adventitial fibroblast • growth • organ culture
This article has been cited by other articles:
 |
|
 |
|
  G. J. Hodges, D. N. Jackson, L. Mattar, J. M. Johnson, and J. K. Shoemaker Neuropeptide Y and neurovascular control in skeletal muscle and skin Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2009; 297(3): R546 - R555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Schlaich, F. Socratous, S. Hennebry, N. Eikelis, E. A. Lambert, N. Straznicky, M. D. Esler, and G. W. Lambert Sympathetic Activation in Chronic Renal Failure J. Am. Soc. Nephrol., May 1, 2009; 20(5): 933 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Danielson Reviving the "biochemical" hypothesis for tendinopathy: new findings suggest the involvement of locally produced signal substances Br. J. Sports Med., April 1, 2009; 43(4): 265 - 268. [Full Text] [PDF]
|
|
|
|
|
|
E Zeisig, B-O Ljung, H Alfredson, and P Danielson Immunohistochemical evidence of local production of catecholamines in cells of the muscle origins at the lateral and medial humeral epicondyles: of importance for the development of tennis and golfer's elbow? Br. J. Sports Med., April 1, 2009; 43(4): 269 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bernini, F. Galetta, F. Franzoni, M. Bardini, C. Taurino, A. Moretti, M. Bernini, P. Berti, P. Miccoli, and A. Salvetti Normalization of catecholamine production following resection of phaeochromocytoma positively influences carotid vascular remodelling Eur. J. Endocrinol., August 1, 2008; 159(2): 137 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Vinci, L. Bellik, S. Filippi, F. Ledda, and A. Parenti Trophic effects induced by {alpha}1D-adrenoceptors on endothelial cells are potentiated by hypoxia Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2140 - H2147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bernini, F. Franzoni, F. Galetta, A. Moretti, C. Taurino, M. Bardini, G. Santoro, L. Ghiadoni, M. Bernini, and A. Salvetti Carotid Vascular Remodeling in Patients with Pheochromocytoma J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1754 - 1760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Erami, H. Zhang, A. Tanoue, G. Tsujimoto, S. A. Thomas, and J. E. Faber Adrenergic catecholamine trophic activity contributes to flow-mediated arterial remodeling Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H744 - H753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Chalothorn, H. Zhang, J. A. Clayton, S. A. Thomas, and J. E. Faber Catecholamines augment collateral vessel growth and angiogenesis in hindlimb ischemia Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H947 - H959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C McGrath, C. Deighan, A. M Briones, M. M. Shafaroudi, M. McBride, J. Adler, S. M Arribas, E. Vila, and C. J Daly New aspects of vascular remodelling: the involvement of all vascular cell types Exp Physiol, July 1, 2005; 90(4): 469 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhang, D. Chalothorn, L. F. Jackson, D. C. Lee, and J. E. Faber Transactivation of Epidermal Growth Factor Receptor Mediates Catecholamine-Induced Growth of Vascular Smooth Muscle Circ. Res., November 12, 2004; 95(10): 989 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, S. Cotecchia, S. A. Thomas, A. Tanoue, G. Tsujimoto, and J. E. Faber Gene deletion of dopamine {beta}-hydroxylase and {alpha}1-adrenoceptors demonstrates involvement of catecholamines in vascular remodeling Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2106 - H2114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Wall, J. E. Faber, X. Yang, M. Tsuzaki, and A. J. Banes Norepinephrine-induced calcium signaling and expression of adrenoceptors in avian tendon cells Am J Physiol Cell Physiol, October 1, 2004; 287(4): C912 - C918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Joles and H. A. Koomans Causes and Consequences of Increased Sympathetic Activity in Renal Disease Hypertension, April 1, 2004; 43(4): 699 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Koomans, P. J. Blankestijn, and J. A. Joles Sympathetic Hyperactivity in Chronic Renal Failure: A Wake-up Call J. Am. Soc. Nephrol., March 1, 2004; 15(3): 524 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bleeke, H. Zhang, N. Madamanchi, C. Patterson, and J. E. Faber Catecholamine-Induced Vascular Wall Growth Is Dependent on Generation of Reactive Oxygen Species Circ. Res., January 9, 2004; 94(1): 37 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Teeters, C. Erami, H. Zhang, and J. E. Faber Systemic alpha 1A-adrenoceptor antagonist inhibits neointimal growth after balloon injury of rat carotid artery Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H385 - H392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Erami, H. Zhang, J. G. Ho, D. M. French, and J. E. Faber alpha 1-Adrenoceptor stimulation directly induces growth of vascular wall in vivo Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1577 - H1587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, C. S. Facemire, A. J. Banes, and J. E. Faber Different alpha -adrenoceptors mediate migration of vascular smooth muscle cells and adventitial fibroblasts in vitro Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2364 - H2370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, C. S. Facemire, A. J. Banes, and J. E. Faber Different alpha -adrenoceptors mediate migration of vascular smooth muscle cells and adventitial fibroblasts in vitro Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2364 - H2370. [Abstract] [Full Text] [PDF]
|
|