Exp Clin Endocrinol Diabetes 2013; 121(09): 551-555
DOI: 10.1055/s-0033-1353183
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Asymmetric Dimethylarginine (ADMA) and Soluble Vascular Cell Adhesion Molecule 1(sVCAM-1) as Circulating Markers for Endothelial Dysfunction in Patients with Pheochromocytoma

V. Vasilev
1   Department of Hypothalamic, Pituitary, Adrenal and Gonadal Diseases, Clinical Centre of Endocrinology, Sofia, Bulgaria
,
J. Matrozova
1   Department of Hypothalamic, Pituitary, Adrenal and Gonadal Diseases, Clinical Centre of Endocrinology, Sofia, Bulgaria
,
A. Elenkova
1   Department of Hypothalamic, Pituitary, Adrenal and Gonadal Diseases, Clinical Centre of Endocrinology, Sofia, Bulgaria
,
S. Vandeva
1   Department of Hypothalamic, Pituitary, Adrenal and Gonadal Diseases, Clinical Centre of Endocrinology, Sofia, Bulgaria
,
G. Kirilov
1   Department of Hypothalamic, Pituitary, Adrenal and Gonadal Diseases, Clinical Centre of Endocrinology, Sofia, Bulgaria
,
S. Zacharieva
1   Department of Hypothalamic, Pituitary, Adrenal and Gonadal Diseases, Clinical Centre of Endocrinology, Sofia, Bulgaria
› Author Affiliations
Further Information

Publication History

received 01 February 2013
first decision 07 June 2013

accepted 29 July 2013

Publication Date:
03 September 2013 (online)

Abstract

Background:

Endothelial dysfunction is a common feature of hypertension and is associated with reduced nitric oxide bioavailability. The endogenous inhibitor of nitric oxide syntase, asymmetric dimethylarginine (ADMA), and soluble adhesion molecules such as vascular cell adhesion molecule 1 (sVCAM-1) have been established as markers of endothelial dysfunction in a number of pathologic conditions including essential hypertension. There is little information, however, about these markers in endocrine hypertension.

Objective:

To investigate the levels of circulating ADMA and sVCAM-1 in patients with pheochromocytoma.

Patients and methods:

Serum ADMA and sVCAM-1 concentrations were assayed by ELISA technique in 18 patients with pheochromocytoma, 18 patients with essential hypertension (EH) and 18 healthy subjects serving as a control group.

Results:

ADMA and sVCAM-1 levels were significantly elevated in pheochromocytoma patients compared to normotensive healthy controls (0.479±0.072 vs. 0.433±0.054 µmol/l, p=0.037 and 690±181 vs. 577±108 ng/ml, p=0.03, respectively). Patients with EH also had higher ADMA concentrations than the control group, but the difference was not significant (0.476±0.075 vs. 0.433±0.054 µmol/l, p=0.06). No associations were found between the levels of ADMA, sVCAM-1 and some potential risk factors for endothelial dysfunction.

Conclusion:

Endothelial function is impaired in patients with pheochromocytoma as indicated by the elevated circulating levels of ADMA and sVCAM-1. The lack of association of these markers with cateholamines, glucose and lipid abnormalities together with their comparable levels in EH patients suggests that endothelial dysfunction is most likely related to hypertension itself.

 
  • References

  • 1 Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980; 288: 373-376
  • 2 Forstermann U, Closs EI, Pollock JS et al. Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Hypertension 1994; 23 (6 Pt 2) 1121-1131
  • 3 Ignarro LJ, Buga GM, Wood KS et al. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 1987; 84: 9265-9269
  • 4 Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 1991; 88: 4651-4655
  • 5 Jeremy JY, Rowe D, Emsley AM et al. Nitric oxide and the proliferation of vascular smooth muscle cells. Cardiovasc Res 1999; 43: 580-594
  • 6 Vallance P, Leone A, Calver A et al. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992; 339: 572-575
  • 7 Wilcken DE, Sim AS, Wang J et al. Asymmetric dimethylarginine (ADMA) in vascular, renal and hepatic disease and the regulatory role of L-arginine on its metabolism. Mol Genet Metab 2007; 91: 309-317 discussion 8
  • 8 Antoniades C, Demosthenous M, Tousoulis D et al. Role of asymmetrical dimethylarginine in inflammation-induced endothelial dysfunction in human atherosclerosis. Hypertension 2011; 58: 93-98
  • 9 Cooke JP. Asymmetrical dimethylarginine: the Uber marker?. Circulation 2004; 109: 1813-1818
  • 10 Sibal L, Agarwal SC, Home PD et al. The Role of Asymmetric Dimethylarginine (ADMA) in Endothelial Dysfunction and Cardiovascular Disease. Curr Cardiol Rev 2010; 6: 82-90
  • 11 Szmitko PE, Wang CH, Weisel RD et al. Biomarkers of vascular disease linking inflammation to endothelial activation: Part II. Circulation 2003; 108: 2041-2048
  • 12 Weber C, Fraemohs L, Dejana E. The role of junctional adhesion molecules in vascular inflammation. Nat Rev Immunol 2007; 7: 467-477
  • 13 Davies MJ, Gordon JL, Gearing AJ et al. The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-selectin in human atherosclerosis. J Pathol 1993; 171: 223-229
  • 14 Boger RH, Bode-Boger SM, Tsao PS et al. An endogenous inhibitor of nitric oxide synthase regulates endothelial adhesiveness for monocytes. J Am Coll Cardiol 2000; 36: 2287-2295
  • 15 Achan V, Broadhead M, Malaki M et al. Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 2003; 23: 1455-1459
  • 16 Perticone F, Sciacqua A, Maio R et al. Asymmetric dimethylarginine, L-arginine, and endothelial dysfunction in essential hypertension. J Am Coll Cardiol 2005; 46: 518-523
  • 17 Wang D, Strandgaard S, Iversen J et al. Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension. Am J Physiol Regul Integr Comp Physiol 2009; 296: R195-R200
  • 18 Perticone F, Sciacqua A, Maio R et al. Endothelial dysfunction, ADMA and insulin resistance in essential hypertension. Int J Cardiol 2010; 142: 236-241
  • 19 Wang H, Liu J. Plasma asymmetric dimethylarginine and L-arginine levels in Chinese patients with essential hypertension without coronary artery disease. J Cardiovasc Dis Res 2011; 2: 177-180
  • 20 Parissis JT, Venetsanou KF, Mentzikof DG et al. Plasma levels of soluble cellular adhesion molecules in patients with arterial hypertension. Correlations with plasma endothelin-1. Eur J Intern Med 2001; 12: 350-356
  • 21 Rizzoni D, Castellano M, Porteri E et al. Vascular structural and functional alterations before and after the development of hypertension in SHR. Am J Hypertens 1994; 7: 193-200
  • 22 Osanai T, Saitoh M, Sasaki S et al. Effect of shear stress on asymmetric dimethylarginine release from vascular endothelial cells. Hypertension 2003; 42: 985-990
  • 23 Rudic RD, Sessa WC. Nitric oxide in endothelial dysfunction and vascular remodeling: clinical correlates and experimental links. Am J Hum Genet 1999; 64: 673-677
  • 24 Higashi Y, Sasaki S, Nakagawa K et al. Excess norepinephrine impairs both endothelium-dependent and -independent vasodilation in patients with pheochromocytoma. Hypertension 2002; 39 (2Pt 2) 513-518
  • 25 Seya Y, Fukuda T, Isobe K et al. Effect of norepinephrine on RhoA, MAP kinase, proliferation and VEGF expression in human umbilical vein endothelial cells. Eur J Pharmacol 2006; 553: 54-60
  • 26 Laycock SK, McMurray J, Kane KA et al. Effects of chronic norepinephrine administration on cardiac function in rats. J Cardiovasc Pharmacol 1995; 26: 584-589
  • 27 Landim MB, Casella Filho A, Chagas AC. Asymmetric dimethylarginine (ADMA) and endothelial dysfunction: implications for atherogenesis. Clinics (Sao Paulo) 2009; 64: 471-478
  • 28 Mallamaci F, Tripepi G, Maas R et al. Analysis of the relationship between norepinephrine and asymmetric dimethyl arginine levels among patients with end-stage renal disease. J Am Soc Nephrol 2004; 15: 435-441
  • 29 Nanayakkara PW, Teerlink T, Stehouwer CD et al. Plasma asymmetric dimethylarginine (ADMA) concentration is independently associated with carotid intima-media thickness and plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration in patients with mild-to-moderate renal failure. Kidney Int 2005; 68: 2230-2236
  • 30 Surdacki A, Nowicki M, Sandmann J et al. Reduced urinary excretion of nitric oxide metabolites and increased plasma levels of asymmetric dimethylarginine in men with essential hypertension. J Cardiovasc Pharmacol 1999; 33: 652-658
  • 31 Chirinos JA, David R, Bralley JA et al. Endogenous nitric oxide synthase inhibitors, arterial hemodynamics, and subclinical vascular disease: the PREVENCION Study. Hypertension 2008; 52: 1051-1059
  • 32 Palomo I, Contreras A, Alarcon LM et al. Elevated concentration of asymmetric dimethylarginine (ADMA) in individuals with metabolic syndrome. Nitric Oxide 2011; 24: 224-228
  • 33 Stuhlinger MC, Abbasi F, Chu JW et al. Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA 2002; 287: 1420-1426
  • 34 Garcia RG, Perez M, Maas R et al. Plasma concentrations of asymmetric dimethylarginine (ADMA) in metabolic syndrome. Int J Cardiol 2007; 122: 176-178
  • 35 Zsuga J, Torok J, Magyar MT et al. Dimethylarginines at the crossroad of insulin resistance and atherosclerosis. Metabolism 2007; 56: 394-399
  • 36 Tummala PE, Chen XL, Sundell CL et al. Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature: A potential link between the renin-angiotensin system and atherosclerosis. Circulation 1999; 100: 1223-1229