Abstract
Angiotensin II and nitric oxide belong to important factors in the functional and structural changes of vessel wall, leading to its increased stiffness. We investigated, whether common mutations of angiotensin II type 1 receptor (AGTR1) and endothelial nitric oxide synthase (eNOS) are associated with increased arterial stiffness. Two polymorphisms, A1166C of AGTR1 and T786C of Enos, were estimated in a random, general population-based sample of 250 subjects. Arterial stiffness was measured using Sphygmocor as aortic (carotid—femoral) and peripheral (femoral—tibial) pulse wave velocities (PWV). Carriers of 3–4 mutant alleles from both polymorphisms, that is, homozygous for both mutations or homozygous for one and heterozygous for the second one, showed significantly higher peripheral PWV (17.92±2.40) than those with none or only 1–2 mutant alleles (12.37±0.51; P<0.003). Carriers of 3–4 mutant alleles had three times higher risk of having increased peripheral PWV (⩾13.63 m s−1, that is, in the top quartile) and this association remained significant after adjustment for potential confounders. No association was found between estimated genotypes and aortic PWV. In conclusion, combination of A1166C of AGTR1 and T786C of eNOS mutations increased stiffness of muscular-type arteries.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001; 37: 1236–1241.
Meaume S, Benetos A, Henry OF, Rudnichi A, Safar ME . Aortic pulse wave velocity predicts cardiovascular mortality in subjects >70 years of age. Arterioscler Thromb Vasc Biol 2001; 21: 2046–2050.
The CAFE Investigators, for the Anglo-Scandinavian Cardiac Outcomes (ASCOT) Investigators. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation 2006; 113: 1213–1225.
Nichols W, O'Rourke MF (eds). Theoretical, experimental and principles. In: AE McDonald's Blood Flow in Arteries, 3rd edn. E Arnold: London, Melbourne, Auckland, 1990, pp. 77–142, 216–269, 269–283, 398–437.
Wuyts FL, Vanhuyse VJ, Langewouters GJ, Decraemer WF, Raman ER, Buyle S . Elastic properties of human aortas in relation to age and atherosclerosis: a structural model. Phys Med Biol 1995; 40: 1577–1597.
Gow BS . The influence of vascular smooth muscle on the viscoelastic properties of blood vessels.In: Bergel DH (ed.) Cardiovascular Fluid Dynamics. Academic Press: London, UK, 1972 pp. 66–97.
Unger T . The role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol 2002; 89: 3A–9A.
Safar ME, Benetos A . Factors influencing arterial stiffness in systolic hypertension in the elderly: role of sodium and the renin-angiotensin system. Am J Hypertens 2003; 16: 249–258.
Stewart AD, Millasseau SC, Kearney MT, Ritter JM, Chowienczyk PJ . Effects of inhibition of basal nitric oxide synthesis on carotid-femoral pulse wave velocity and augmentation index in humans. Hypertension 2003; 42: 915–918.
Wilkinson IB, Qasem A, McEniery CM, Webb DJ, Avolio AP, Cockcroft JR . Nitric oxide regulates local arterial distensibility in vivo. Circulation 2002; 105: 213–217.
Bank AJ, Kaiser DR, Rajala S, Cheng A . In vivo human brachial artery elastic mechanics: effects of smooth muscle relaxation. Circulation 1999; 100: 41–47.
Bonnardeaux A, Davies E, Jeunemaitre X, Fery I, Charru A, Clauser E et al. Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 1994; 24: 63–69.
Castellano M, Muiesan ML, Beschi M, Rizzoni D, Cinelli A, Salvetti M et al. Angiotensin II type 1 receptor A/C1166 polymorphism. Relationships with blood pressure and cardiovascular structure. Hypertension 1996; 28: 1076–1080.
Tiret L, Blanc H, Ruidavets JB, Arveiler D, Luc G, Jeunemaitre X et al. Gene polymorphism of the renin-angiotensin system in relation to hypertension and parental history of myocardial infarction and stroke: the PEGASE study. J Hypertens 1998; 16: 37–44.
Ghilardi G, Biondi ML, DeMonti M, Bernini M, Turri O, Massaro F et al. Independent risk factor for moderate to severe internal carotid artery stenosis: T786C mutation of the endothelial nitric oxide synthase gene. Clin Chem 2002; 48: 989–993.
Cífková R, Cíkodová Z, Lánská V, Adámková V, Novozámská E, Petržílková Z . Trends in blood pressure levels, prevalence, awareness, treatment, and control of hypertension in the Czech population from 1985 to 2000/01. J Hypertens 2004; 22: 1479–1485.
Mayer O, Filipovský J, Dolejšová M, Cífková R, Šimon J, Bolek L . Mild hyperhomocysteinaemia is associated with increased aortic stiffness in general population. J Hum Hypertens 2006; 20: 267–271.
Filipovsky J, Ticha M, Cifkova R, Lanska V, Stastna V, Roucka P . Large artery stiffness and pulse wave reflection: results of a population-based study. Blood Press 2005; 14: 45–52.
Wilkinson IB, Fuchs SA, Jansen IM, Spratt JC, Murray GD, Cockcroft JR et al. Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis. J Hypertens 1998; 16: 2079–2084.
Katsuya T, Koike G, Yee TW, Sharpe N, Jackson R, Norton R et al. Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease. Lancet 1995; 345: 1600–1603.
Alvarez R, Gonzalez P, Batalla A, Reguero JR, Iglesias-Cubero G, Hevia S et al. Association between the NOS3 (−786 T/C) and the ACE (I/D) DNA genotypes and early coronary artery disease. Nitric Oxide 2001; 5: 343–348.
Boulanger CM, Caputo L, Levy BI . Endothelial AT1-mediated release of nitric oxide decreases angiotensin II contractions in rat carotid artery. Hypertension 1995; 26: 752–757.
Pueyo ME, Arnal JF, Rami J, Michel JB . Angiotensin II stimulates the production of NO and peroxynitrite in endothelial cells. Am J Physiol 1998; 274: C214–C220.
Fitch RM, Rutledge JC, Wang YX, Powers AF, Tseng JL, Clary T et al. Synergistic effect of angiotensin II and nitric oxide synthase inhibitor in increasing aortic stiffness in mice. Am J Physiol Heart Circ Physiol 2006; 290: H1190–H1198.
Benetos A, Topouchian J, Ricard S, Gautier S, Bonnardeaux A, Asmar R et al. Influence of angiotensin II type 1 receptor polymorphism on aortic stiffness in never-treated hypertensive patients. Hypertension 1995; 26: 44–47.
Benetos A, Gautier S, Ricard S, Topouchian J, Asmar R, Poirier O et al. Influence of angiotensin-converting enzyme and angiotensin II type 1 receptor gene polymorphisms on aortic stiffness in normotensive and hypertensive patients. Circulation 1996; 94: 698–703.
Lajemi M, Labat C, Gautier S, Lacolley P, Safar M, Asmar R et al. Angiotensin II type 1 receptor-153A/G and 1166A/C gene polymorphisms and increase in aortic stiffness with age in hypertensive subjects. J Hypertens 2001; 19: 407–413.
Rehman A, Rasool AH, Naing L, Roshan TM, Rahman AR . Influence of the angiotensin II type I receptor gene 1166A>C polymorphism on BP and aortic pulse wave velocity among Malays. Ann Hum Genet 2007; 71: 86–95.
Gardier S, Vincent M, Lantelme P, Rial MO, Bricca G, Milon H . A1166C polymorphism of angiotensin II type 1 receptor, blood pressure and arterial stiffness in hypertension. J Hypertens 2004; 22: 2135–2142.
Chen W, Srinivasan SR, Bond MG, Tang R, Urbina EM, Li S et al. Nitric oxide synthase gene polymorphism (G894T) influences arterial stiffness in adults: the Bogalusa Heart Study. Am J Hypertens 2004; 17: 553–559.
Benetos A, Laurent S, Hoeks AP, Boutouyrie P, Safar ME . Arterial alterations with ageing and high blood pressure. A noninvasive study of carotid and femoral arteries. Arterioscler Thromb 1993; 13: 90–97.
van der Heijden-Spek JJ, Staessen JA, Fagard RH, Hoeks AP, Boudier HA, van Bortel LM . Effect of age on brachial artery wall properties differs from the aorta and is gender dependent: a population study. Hypertension 2000; 35: 637–642.
Acknowledgements
The present study was founded by Internal Grant Agency of Czech Ministry of Health (grant no. 9333–3) and by Ministry of Education (grant no. 0021620819). We also used several data from post-MONICA study therefore we would like to acknowledge the cooperation of all investigators who participated on this survey.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mayer, O., Filipovský, J., Pešta, M. et al. Synergistic effect of angiotensin II type 1 receptor and endothelial nitric oxide synthase gene polymorphisms on arterial stiffness. J Hum Hypertens 22, 111–118 (2008). https://doi.org/10.1038/sj.jhh.1002279
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.jhh.1002279
Keywords
This article is cited by
-
Association between AT1 receptor gene polymorphism and left ventricular hypertrophy and arterial stiffness in essential hypertension patients: a prospective cohort study
BMC Cardiovascular Disorders (2022)
-
A Review of Vascular Traits and Assessment Techniques, and Their Heritability
Artery Research (2022)
-
Genetic Determinants of Arterial Stiffness
Journal of Cardiovascular Translational Research (2015)
-
A Review of Genetics, Arterial Stiffness, and Blood Pressure in African Americans
Journal of Cardiovascular Translational Research (2012)
-
Pulse pressure: more than 100 years of changes in stroke volume
Intensive Care Medicine (2011)