Abstract
Flow-mediated dilation (FMD) is a widely used tool to investigate endothelial function. However, FMD assessment may cause mechanical damage to the arterial endothelium. In this study we investigated the effect of FMD assessment on endothelial function. We studied 20 healthy subjects (26 ± 6 years; 12 males). FMD was assessed by measuring brachial artery dilation in response to hyperemia after 5 min of forearm cuff inflation. Subjects were studied on 2 subsequent days. On day 1 they underwent two consecutive FMD measures, with the second test (FMD2) performed 15 min after the first test (FMD1). On day 2, the subjects were randomized to receive either placebo (saline) or intravenous l-arginine (10 g in 20 min). At the end of the infusion, patients underwent two consecutive FMD measures following the same protocol as on day 1. Asymmetric dimethyl-arginine (ADMA) serum levels were assessed on day 2 before FMD1 and FMD2. On day 1, FMD2 was lower than FMD1 in both groups (placebo 6.47 ± 2.1 vs. 7.86 ± 1.8%, P < 0.01; arginine 6.13 ± 2.6 vs. 7.76 ± 2.7%, P < 0.01). On day 2, a significant reduction of FMD was observed during FMD2 compared to FMD1 in the placebo group (5.82 ± 1.7 vs. 7.44 ± 2.2%, P < 0.001), but not in the arginine group (7.19 ± 1.5 vs. 7.27 ± 1.5, P = 0.67). ADMA levels significantly increased compared to baseline after FMD1 (0.59 ± 0.12–0.91 ± 0.64 μmol/l, P = 0.036), with similar changes in the two groups. FMD assessment induces a significant impairment of endothelial function. An increase of endogenous NO synthesis inhibitors seems responsible for the phenomenon that is reversed by l-arginine administration.
Similar content being viewed by others
References
Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 115:1111–1115
Dimitrijevic I, Ekelund U, Edvinsson ML, Edvinsson L (2009) Increased expression of endothelin ET(B) and angiotensin AT(1) receptors in peripheral resistance arteries of patients with suspected acute coronary syndrome. Heart Vessels 24:393–398
Song BG, Park JB, Cho SJ, Lee SY, Kim JH, Choi SM, Park JH, Park YH, Choi JO, Lee SC, Park SW (2009) Pulse wave velocity is more closely associated with cardiovascular risk than augmentation index in the relatively low-risk population. Heart Vessels 24:413–418
Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R, International Brachial Artery Reactivity Task Force (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilatation of the brachial artery. A report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39:257–265
Rubanyi GM, Romero JC, Vanhoutte PM (1986) Flow-induced release of endothelium-derived relaxing factor. Am J Physiol 250:H1145–H1149
Oyama J, Satoh S, Suematsu N, Kadokami T, Maeda T, Sugano M, Makino N (2010) Scavenging free radicals improves endothelial dysfunction in human coronary arteries in vivo. Heart Vessels 25:379–385
Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T (2001) Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 104:2673–2678
Kitta Y, Obata JE, Nakamura T, Hirano M, Kodama Y, Fujioka D, Saito Y, Kawabata K, Sano K, Kobayashi T, Yano T, Nakamura K, Kugiyama K (2009) Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease. J Am Coll Cardiol 53:323–330
Tomiyama H, Matsumoto C, Yamada J, Teramoto T, Abe K, Ohta H, Kiso Y, Kawauchi T, Yamashina A (2008) The relationships of cardiovascular disease risk factors to flow-mediated dilatation in Japanese subjects free of cardiovascular disease. Hypertens Res 31:2019–2025
Juonala M, Kähönen M, Laitinen T, Hutri-Kähönen N, Jokinen E, Taittonen L, Pietikäinen M, Helenius H, Viikari JS, Raitakari OT (2008) Effect of age and sex on carotid intima-media thickness, elasticity and brachial endothelial function in healthy adults: the Cardiovascular Risk in Young Finns Study. Eur Heart J 29:1198–1206
Moens AL, Goovaerts I, Claeys MJ, Vrints CJ (2005) Flow-mediated vasodilation: a diagnostic instrument, or an experimental tool? Chest 127:2254–2263
Gottdiener JS, Kop WJ, Hausner E, McCeney MK, Herrington D, Krantz DS (2003) Effects of mental stress on flow-mediated brachial arterial dilation and influence of behavioral factors and hypercholesterolemia in subjects without cardiovascular disease. Am J Cardiol 92:87–91
Clarkson P, Montgomery HE, Mullen MJ, Donald AE, Powe AJ, Bull T, Jubb M, World M, Deanfield JE (1999) Exercise training enhances endothelial function in young men. J Am Coll Cardiol 33:1379–1385
Saihara K, Hamasaki S, Ishida S, Kataoka T, Yoshikawa A, Orihara K, Ogawa M, Oketani N, Fukudome T, Atsuchi N, Shinsato T, Okui H, Kubozono T, Ichiki H, Kuwahata S, Mizoguchi E, Fujita S, Takumi T, Ninomiya Y, Tomita K, Tei C (2010) Enjoying hobbies is related to desirable cardiovascular effects. Heart Vessels 25:113–120
Gemignani V, Faita F, Ghiadoni L, Poggianti E, Demi M (2007) A system for real-time measurement of the brachial artery diameter in B-mode ultrasound images. IEEE Trans Med Imaging 26:393–404
Vallance P, Leone A, Calver A, Collier J, Moncada S (1992) Accumulation of an endogenous inhibitor of NO synthesis in chronic renal failure. Lancet 339:572–575
Thijssen DHJ, Dawson EA, Tinken TM, Cable NT, Green DJ (2009) Retrograde flow and shear rate acutely impair endothelial function in humans. Hypertension 53:986–992
Asagami T, Abbasi F, Stuelinger M, Lamendola C, McLaughlin T, Cooke JP, Reaven GM, Tsao PS (2002) Metformin treatment lowers asymmetric dimethylarginine concentrations in patients with type 2 diabetes. Metabolism 51:843–846
Lin KY, Ito A, Asagami T, Tsao PS, Adimoolam S, Kimoto M, Tsuji H, Reaven GM, Cooke JP (2002) Impaired nitric oxide synthase pathway in diabetes mellitus: role of asymmetric dimethylarginine and dimethylarginine dimethylaminohydrolase. Circulation 106:987–992
Valkonen VP, Paiva H, Salonen JT, Lakka TA, Lehtimaki T, Laakso J, Laaksonen R (2001) Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet 358:2127–2128
Cooke JP (2000) Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 20:2032–2037
Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP (1999) Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 99:3092–3095
Vallance P, Leiper J (2004) Cardiovascular biology of the asymmetric dimethylarginine:dimethylarginine dimethylaminohydrolase pathway. Arterioscler Thromb Vasc Biol 24:1023–1030
Azuma H, Sato J, Hamasaki H, Sugimoto A, Isotani E, Obayashi S (1995) Accumulation of endogenous inhibitors for nitric oxide synthesis and decreased content of l-arginine in regenerated endothelial cells. Br J Pharmacol 115:1001–1004
Osanai T, Saitoh M, Sasaki S, Tomita H, Matsunaga T, Okumura K (2003) Effect of shear stress on asymmetric dimethylarginine release from vascular endothelial cells. Hypertension 42:985–990
Bai Y, Sun L, Yang T, Sun K, Chen J, Hui R (2009) Increase in fasting vascular endothelial function after short-term oral l-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials. Am J Clin Nutr 89:77–84
Böger RH (2004) Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the “l-arginine paradox” and acts as a novel cardiovascular risk factor. J Nutr 134:2842S–2847S
Böger RH, Bode-Böger SM (2001) The clinical pharmacology of l-arginine. Annu Rev Pharmacol Toxicol 41:79–99
Forrest CR, Neligan P, Zhong A, He W, Yang RZ, Pang CY (1997) Acute adenosine treatment is effective in augmentation of ischemic tolerance in muscle flaps in the pig. Plast Reconstr Surg 99:172–182
Auchampach JA, Gross GJ (1993) Adenosine A1 receptors, KATP channels, and ischemic preconditioning in dogs. Am J Physiol 264:H1327–H1336
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nerla, R., Di Monaco, A., Sestito, A. et al. Transient endothelial dysfunction following flow-mediated dilation assessment. Heart Vessels 26, 524–529 (2011). https://doi.org/10.1007/s00380-010-0087-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00380-010-0087-z