Published: 2017-01-05

Non-invasive evaluation of endothelial function in healthy Indian participants using tonometry

Chinthaparthi Prabhakar Reddy, MUR Naidu


Background: Vascular endothelium releases number of biological active mediators, including nitric oxide (NO) that regulates vessel tone. Endothelial dysfunction is independent risk factor for cardiovascular disease. The study was done to assess endothelial function by augmentation index (AIx) calculated from derived aortic wave forms using radial pulse wave analysis (PWA) with provocative pharmacological testing, measured in response to endothelium independent, direct stimulus with nitrovasodilator nitroglycerine (NTG) and endothelium dependent activation of L-arginine-NO-pathway by salbutomol.

Methods: Eighteen healthy subjects participated in the study. Radial artery wave forms were recorded with a high-fidelity tonometer (Sphygmocor, AtCor medicals, Australia). Recordings were taken at baseline and after 3, 5, 10, 15 and 20 minutes of NTG (0.5 mg) sublingual administration, and at baseline and after 5, 10, 15 and 20 minutes of salbutomol (400 µg) inhalation.

Results: Mean age was 25±2.4 years and body mass index 24±2.5 kg/m2 of study subjects. Salbutomol and NTG significantly reduced AIx at all-time points (salbutomol: baseline 7.6%, 5 minutes -3.6%, 10 minutes -5.8%, 15 minutes -7.8% and 20 minutes -3.6%, p ≤0.05 and NTG baseline 8.4%, 3 minutes -3.2%, 5 minutes -7.7%, 10 minutes -9.7%, 15 minutes -11.2% and 20 minutes -8.6%, p ≤0.001). The effect of provocative pharmacological testing on heart rate, aortic and radial pressures, mean arterial pressure and pulse pressure was not altered (p≥0.05).

Conclusions: This method of assessing endothelial function, which appears before onset of clinical signs and symptoms and is a simple, convenient, quick method.


Endothelial function, Nitric oxide, Pulse wave analysis, Augmentation index, Salbutamol, Nitroglycerine

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Esper RJ, Nordaby RA, Vilariño JO, Paragano A, Cacharrón JL, Machado RA. Endothelial dysfunction: a comprehensive appraisal. Cardiovascular Diabetology. 2006;5:4.

Barac A, Campia U, Panza JA. Methods for evaluating endothelial function in humans. Hypertension. 2007;49;748-60.

Treasure CB, Klein JL, Vita JA, Manoukian SV, Renwick GH, Selwyn AP, et al. Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels. Circulation. 1993;87:86-93.

Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986;315:1046-51.

Cox DA, Vita JA, Treasure CB, Fish RD, Alexander RW, Ganz P, et al. Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans. Circulation. 1989;80:458-65.

Drexler H, Zeiher AM, Wollschlager H, Meinertz T, Just H, Bonzel T. Flow-dependent coronary artery dilatation in humans. Circulation. 1989;80:466-74.

Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111-5.

Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the. International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002;39:257-65.

Whitney RJ. The measurement of volume changes in human limbs. J Physiol. 1953;121:1-27.

Greenfield AD, Whitney RJ, Mowbray JF. Methods for the investigation of peripheral blood flow. Br Med Bull. 1963;19:101-09.

Cracowski JL, Minson CT, Salvat-Melis M, Halliwill JR. Methodological issues in the assessment of skin microvascular endothelial function in humans. Trends Pharmacol Sci. 2006;27:503-8.

Vasan RS. Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation. 2006;113:2335-62.

Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348:593- 600.

Hristov M, Erl W, Weber PC. Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol. 2003;23:1185-9.

Jones LC, Hingorani AD. Genetic regulation of endothelial function. Heart. 2005;91:1275-7.

Mannucci PM. von Willebrand factor: a marker of endothelial damage? Arterioscler Thromb Vasc Biol. 1998;18:1359-62.

Hrafnkelsdottir T, Wall U, Jern C, Jern S. Impaired capacity for endogenous fibrinolysis in essential hypertension. Lancet. 1998;352:1597-8.

Oliver JJ, Webb DJ, Newby DE. Stimulated tissue plasminogen activator release as a marker of endothelial function in humans. Arterioscler Thromb Vasc Biol. 2005;25:2470-9.

Thogersen AM, Jansson JH, Boman K, Nilsson TK, Weinehall L, Huhtasaari F, et al. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Circulation. 1998;98:2241-7.

Malik I, Danesh J, Whincup P, Bhatia V, Papacosta O, Walker M, et al. Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis. Lancet. 2001;358:971-6.

Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. 2003;107:363-9.

Marcelo LG, Haynes WG. Arterial compliance and endothelial function. Current Diabetes Reports. 2007;7:269-75.

Hayward CS, Kraidly M, Webb CM, Collins P. Assessment of endothelial function using peripheral waveform analysis: a clinical application. J Am Coll Cardiol. 2002;40:521-8.

Chowienczyk PJ, Kelly RP, MacCallum H, Millasseau SC, Andersson TL, Gosling RG, et al. Photoplethysmographic assessment of pulse wave reflection: blunted response to endotheliumdependent beta 2-adrenergic vasodilation in type II diabetes mellitus. J Am Coll Cardiol. 1999;34:2007-014.

Wilkinson IB, Hall IR, MacCallum H, Mackenzie IS, McEniery CM, van der Arend BJ, et al. Pulse-wave analysis: clinical evaluation of a noninvasive, widely applicable method for assessing endothelial function. Arterioscler Thromb Vasc Biol. 2002;22:147-52.