This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dubey, R. K. Articles by Jackson, E. K. Search for Related Content PubMed PubMed Citation Articles by Dubey, R. K. Articles by Jackson, E. K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-PROLINE

(Hypertension. 1999;33:190-194.)
© 1999 American Heart Association, Inc.

Scientific Contribution

Adenosine Inhibits Collagen and Total Protein Synthesis in Vascular Smooth Muscle Cells

Presented at the Annual American Heart Association Meeting for Council for High Blood Pressure, Philadelphia, September 1998, and published in abstract form (Hypertension, 1998).

Raghvendra K. Dubey; Delbert G. Gillespie; Edwin K. Jackson

Correspondence to Dr Raghvendra K. Dubey, Center for Clinical Pharmacology, 623 Scaife Hall, 200 Lothrop Street, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA. E-mail dubey{at}novell2.dept-med.pitt.edu

Abstract—The objective of this study was to characterize the effects of exogenous, drug-induced and cAMP-adenosine pathway–derived adenosine on collagen synthesis by and hypertrophy of vascular smooth muscle cells (SMCs). Confluent vascular SMCs were stimulated with 2.5% fetal calf serum in the presence and absence of adenosine receptor agonists [adenosine, 2-chloroadenosine, N⁶-cyclopentyladenosine, 5'-N-ethylcarboxamidoadenosine, 5'-N-methylcarboxamidoadenosine, and 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamino adenosine], drugs that increase levels of endogenous adenosine [erythro-9-(2-hydroxy-3-nonyl) adenine, dipyridamole, and iodotubericidin], and cAMP (increases adenosine by conversion to AMP and hence to adenosine via the cAMP-adenosine pathway). Adenosine receptor agonists inhibited fetal calf serum-induced collagen and total protein synthesis (as assessed by [³H]proline and [³H]leucine incorporation, respectively) with a relative potency profile consistent with the effects being mediated by adenosine A_2B receptors. Erythro-9-(2-hydroxy-3-nonyl) adenine, dipyridamole, iodotubericidin, and cAMP also inhibited collagen and total protein synthesis. The effects of 2-chloroadenosine, erythro-9-(2-hydroxy-3-nonyl) adenine, iodotubericidin, and cAMP on collagen and total protein synthesis were attenuated by KF17837 and 1,3-dipropyl-8-p-sulfophenylxanthine (selective and nonselective A₂ receptor antagonists, respectively) but not by 8-cyclopentyl-1,3-dipropylxanthine (selective A₁ receptor antagonist). These studies indicate that exogenous, drug-induced and cAMP-adenosine pathway–derived adenosine inhibit vascular SMC collagen synthesis and hypertrophy via A_2B receptors. Thus, exogenous A_2B receptor agonists and drugs that modulate endogenous adenosine levels may protect against vasoocclusive disorders by attenuating extracellular matrix synthesis by and cellular hypertrophy of vascular SMCs. Moreover, the cAMP-adenosine pathway may protect against vascular hypertrophy.

Key Words: adenosine • muscle, smooth • extracellular matrix • collagen • hypertrophy

This article has been cited by other articles:

				D. Yang, M. Koupenova, D. J. McCrann, K. J. Kopeikina, H. M. Kagan, B. M. Schreiber, and K. Ravid The A2b adenosine receptor protects against vascular injury PNAS, January 15, 2008; 105(2): 792 - 796. [Abstract] [Full Text] [PDF]

				W. P. Robinson III, C. D. Douillet, P. M. Milano, R. C. Boucher, C. Patterson, and P. B. Rich ATP stimulates MMP-2 release from human aortic smooth muscle cells via JNK signaling pathway Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1988 - H1996. [Abstract] [Full Text] [PDF]

				J. Shen, S. P. Halenda, M. Sturek, and P. A. Wilden Novel Mitogenic Effect of Adenosine on Coronary Artery Smooth Muscle Cells: Role for the A1 Adenosine Receptor Circ. Res., May 13, 2005; 96(9): 982 - 990. [Abstract] [Full Text] [PDF]

				J. Asbun, A. M. Manso, and F. J. Villarreal Profibrotic influence of high glucose concentration on cardiac fibroblast functions: effects of losartan and vitamin E Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H227 - H234. [Abstract] [Full Text] [PDF]

				J. P. Headrick, B. Hack, and K. J. Ashton Acute adenosinergic cardioprotection in ischemic-reperfused hearts Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H1797 - H1818. [Abstract] [Full Text] [PDF]

				N. P. Riksen, G. A. Rongen, H. J. Blom, F. G.M. Russel, G. H.J. Boers, and P. Smits Potential role for adenosine in the pathogenesis of the vascular complications of hyperhomocysteinemia Cardiovasc Res, August 1, 2003; 59(2): 271 - 276. [Abstract] [Full Text] [PDF]

				R. S. Ostrom, J. E. Naugle, M. Hase, C. Gregorian, J. S. Swaney, P. A. Insel, L. L. Brunton, and J. G. Meszaros Angiotensin II Enhances Adenylyl Cyclase Signaling via Ca2+/Calmodulin: Gq-Gs CROSS-TALK REGULATES COLLAGEN PRODUCTION IN CARDIAC FIBROBLASTS J. Biol. Chem., June 27, 2003; 278(27): 24461 - 24468. [Abstract] [Full Text] [PDF]

				B. Jian, J. Xu, J. Connolly, R. C. Savani, N. Narula, B. Liang, and R. J. Levy Serotonin Mechanisms in Heart Valve Disease I: Serotonin-Induced Up-Regulation of Transforming Growth Factor-{beta}1 via G-Protein Signal Transduction in Aortic Valve Interstitial Cells Am. J. Pathol., December 1, 2002; 161(6): 2111 - 2121. [Abstract] [Full Text] [PDF]

				E. K. Jackson, C. Zhu, and S. P. Tofovic Expression of adenosine receptors in the preglomerular microcirculation Am J Physiol Renal Physiol, July 1, 2002; 283(1): F41 - F51. [Abstract] [Full Text] [PDF]

				G. Burnstock Purinergic Signaling and Vascular Cell Proliferation and Death Arterioscler Thromb Vasc Biol, March 1, 2002; 22(3): 364 - 373. [Abstract] [Full Text] [PDF]

				E. K. Jackson and R. K. Dubey Role of the extracellular cAMP-adenosine pathway in renal physiology Am J Physiol Renal Physiol, October 1, 2001; 281(4): F597 - F612. [Abstract] [Full Text] [PDF]

				J. G. Webb, P. W. Yates, Q. Yang, Y. V. Mukhin, and S. M. Lanier Adenylyl cyclase isoforms and signal integration in models of vascular smooth muscle cells Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1545 - H1552. [Abstract] [Full Text] [PDF]

				R. K. Dubey, D. G. Gillespie, Z. Mi, and E. K. Jackson Endogenous Cyclic AMP-Adenosine Pathway Regulates Cardiac Fibroblast Growth Hypertension, April 1, 2001; 37(4): 1095 - 1100. [Abstract] [Full Text] [PDF]

				E. K. Jackson and Z. Mi Preglomerular Microcirculation Expresses the cAMP-Adenosine Pathway J. Pharmacol. Exp. Ther., October 1, 2000; 295(1): 23 - 28. [Abstract] [Full Text]