(Circulation. 1995;91:1314-1319.)
© 1995 American Heart Association, Inc.
Articles |
Nitric Oxide Is Responsible for Flow-Dependent Dilatation of Human Peripheral Conduit Arteries In Vivo
From the Department of Pharmacology, VACOMED, IFRMP, Rouen University Medical School and Rouen Hospital (France) (R.J., V.R., E.H.B., C.T.) and the Department of Clinical Pharmacology, Basel University Hospital (Switzerland) (W.E.H., L.L., T.F.L.).
Correspondence to T.F. Lüscher, MD, Cardiology, University Hospital, CH 4031, Bern, Switzerland.
Background Experimental evidence suggests that flow-dependent dilatation of conduit arteries is mediated by nitric oxide (NO) and/or prostacyclin. The present study was designed to assess whether NO or prostacyclin also contributes to flow-dependent dilatation of conduit arteries in humans.
Methods and Results Radial artery internal diameter (ID) was measured continuously in 16 healthy volunteers (age, 24±1 years) with a transcutaneous A-mode echo-tracking system coupled to a Doppler device for the measurement of radial blood flow. In 8 subjects, a catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 8 µmol/min for 7 minutes; infusion rate, 0.8 mL/min). Flow-dependent dilatation was evaluated before and after L-NMMA or aspirin as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3-minute cuff wrist occlusion). Under control conditions, release of the occlusion induced a marked increase in radial blood flow (from 24±3 to 73±11 mL/min; P<.01) followed by a delayed increase in radial diameter (flow-mediated dilatation; from 2.67±0.10 to 2.77±0.12 mm; P<.01) without any change in heart rate or arterial pressure. L-NMMA decreased basal forearm blood flow (from 24±3 to 13±3 mL/min; P<.05) without affecting basal radial artery diameter, heart rate, or arterial pressure, whereas aspirin (1 g PO) was without any hemodynamic effect. In the presence of L-NMMA, the peak flow response during hyperemia was not affected (76±12 mL/min), but the duration of the hyperemic response was markedly reduced, and the flow-dependent dilatation of the radial artery was abolished and converted to a vasoconstriction (from 2.62±0.11 to 2.55±0.11 mm; P<.01). In contrast, aspirin did not affect the hyperemic response nor the flow-dependent dilatation of the radial artery.
Conclusions The present investigation demonstrates that NO, but not prostacyclin, is essential for flow-mediated dilatation of large human arteries. Hence, this response can be used as a test for the L-arginine/NO pathway in clinical studies.
Key Words: blood flow • endothelium-derived factors • L-NMMA • arteries • dilation
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 H. Schroeter, C. Heiss, J. Balzer, P. Kleinbongard, C. L. Keen, N. K. Hollenberg, H. Sies, C. Kwik-Uribe, H. H. Schmitz, and M. Kelm (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans PNAS, January 24, 2006; 103(4): 1024 - 1029. [Abstract] [Full Text] [PDF]
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H. Kocak, K. Ceken, A. Yavuz, S. Yucel, A. Gurkan, O. Erdogan, F. Ersoy, G. Yakupoglu, A. Demirbas, and M. Tuncer Effect of renal transplantation on endothelial function in haemodialysis patients Nephrol. Dial. Transplant., January 1, 2006; 21(1): 203 - 207. [Abstract] [Full Text] [PDF]
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R. P. Bochmann, W. Seibel, E. Haase, V. Hietschold, H. Rodel, and A. Deussen External compression increases forearm perfusion J Appl Physiol, December 1, 2005; 99(6): 2337 - 2344. [Abstract] [Full Text] [PDF]
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N. Nair, R. K Oka, L. D Waring, E. M Umoh, C B. Taylor, and J. P Cooke Vascular compliance versus flow-mediated vasodilation: correlation with cardiovascular risk factors Vascular Medicine, November 1, 2005; 10(4): 275 - 283. [Abstract] [PDF]
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K. E Pyke and M. E Tschakovsky The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function J. Physiol., October 15, 2005; 568(2): 357 - 369. [Abstract] [Full Text] [PDF]
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C. Heiss, P. Kleinbongard, A. Dejam, S. Perre, H. Schroeter, H. Sies, and M. Kelm Acute Consumption of Flavanol-Rich Cocoa and the Reversal of Endothelial Dysfunction in Smokers J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1276 - 1283. [Abstract] [Full Text] [PDF]
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R. Joannides and J. Bellien Flow-mediated dilatation revisited J Appl Physiol, October 1, 2005; 99(4): 1623 - 1623. [Abstract] [Full Text] [PDF]
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 M. A. Sackner, E. Gummels, and J. A. Adams Effect of Moderate-Intensity Exercise, Whole-Body Periodic Acceleration, and Passive Cycling on Nitric Oxide Release Into Circulation Chest, October 1, 2005; 128(4): 2794 - 2803. [Abstract] [Full Text] [PDF]
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D. Green Point: Flow-mediated dilation does reflect nitric oxide-mediated endothelial function J Appl Physiol, September 1, 2005; 99(3): 1233 - 1234. [Full Text] [PDF]
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M. E. Tschakovsky and K. E. Pyke Counterpoint: Flow-mediated dilation does not reflect nitric oxide-mediated endothelial function J Appl Physiol, September 1, 2005; 99(3): 1235 - 1237. [Full Text] [PDF]
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REBUTTAL FROM DR. GREEN J Appl Physiol, September 1, 2005; 99(3): 1237 - 1237. [Full Text] [PDF]
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REBUTTAL FROM DRS. TSCHAKOVSKY AND PYKE J Appl Physiol, September 1, 2005; 99(3): 1237 - 1238. [Full Text] [PDF]
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J. Hetzel, B. Balletshofer, K. Rittig, D. Walcher, W. Kratzer, V. Hombach, H.-U. Haring, W. Koenig, and N. Marx Rapid Effects of Rosiglitazone Treatment on Endothelial Function and Inflammatory Biomarkers Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 1804 - 1809. [Abstract] [Full Text] [PDF]
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E. D. Beishuizen, J. T. Tamsma, J. W. Jukema, M. A. van de Ree, J. C. M. van der Vijver, A. E. Meinders, and M. V. Huisman The Effect of Statin Therapy on Endothelial Function in Type 2 Diabetes Without Manifest Cardiovascular Disease Diabetes Care, July 1, 2005; 28(7): 1668 - 1674. [Abstract] [Full Text] [PDF]
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K. Sydow, C. E Mondon, and J. P Cooke Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA Vascular Medicine, July 1, 2005; 10(1_suppl): S35 - S43. [Abstract] [PDF]
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J. Bellien, R. Joannides, M. Iacob, P. Arnaud, and C. Thuillez Calcium-Activated Potassium Channels and NO Regulate Human Peripheral Conduit Artery Mechanics Hypertension, July 1, 2005; 46(1): 210 - 216. [Abstract] [Full Text] [PDF]
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D. R. Witte, J. Westerink, E. J. de Koning, Y. van der Graaf, D. E. Grobbee, and M. L. Bots Is the Association Between Flow-Mediated Dilation and Cardiovascular Risk Limited to Low-Risk Populations? J. Am. Coll. Cardiol., June 21, 2005; 45(12): 1987 - 1993. [Abstract] [Full Text] [PDF]
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M. S. O'Neill, A. Veves, A. Zanobetti, J. A. Sarnat, D. R. Gold, P. A. Economides, E. S. Horton, and J. Schwartz Diabetes Enhances Vulnerability to Particulate Air Pollution-Associated Impairment in Vascular Reactivity and Endothelial Function Circulation, June 7, 2005; 111(22): 2913 - 2920. [Abstract] [Full Text] [PDF]
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 L. R. Sajja, G. Mannam, N. R. Pantula, and S. Sompalli Role of Radial Artery Graft in Coronary Artery Bypass Grafting Ann. Thorac. Surg., June 1, 2005; 79(6): 2180 - 2188. [Abstract] [Full Text] [PDF]
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A. L. Moens, I. Goovaerts, M. J. Claeys, and C. J. Vrints Flow-Mediated Vasodilation: A Diagnostic Instrument, or an Experimental Tool? Chest, June 1, 2005; 127(6): 2254 - 2263. [Abstract] [Full Text] [PDF]
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K. Sydow, C. E Mondon, and J. P Cooke Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA Vascular Medicine, May 1, 2005; 10(2_suppl): S35 - S43. [Abstract] [PDF]
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B. R. Clapp, G. M. Hirschfield, C. Storry, J. R. Gallimore, R. P. Stidwill, M. Singer, J. E. Deanfield, R. J. MacAllister, M. B. Pepys, P. Vallance, et al. Inflammation and Endothelial Function: Direct Vascular Effects of Human C-Reactive Protein on Nitric Oxide Bioavailability Circulation, March 29, 2005; 111(12): 1530 - 1536. [Abstract] [Full Text] [PDF]
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M. R. Skilton, N. T. Lai, K. A. Griffiths, L. M. Molyneaux, D. K. Yue, D. R. Sullivan, and D. S. Celermajer Meal-related increases in vascular reactivity are impaired in older and diabetic adults: insights into roles of aging and insulin in vascular flow Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1404 - H1410. [Abstract] [Full Text] [PDF]
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C. Giannattasio, A. Zoppo, G. Gentile, M. Failla, A. Capra, F.M. Maggi, A. Catapano, and G. Mancia Acute Effect of High-Fat Meal on Endothelial Function in Moderately Dyslipidemic Subjects Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 406 - 410. [Abstract] [Full Text] [PDF]
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S. D. Katz, K. Hryniewicz, I. Hriljac, K. Balidemaj, C. Dimayuga, A. Hudaihed, and A. Yasskiy Vascular Endothelial Dysfunction and Mortality Risk in Patients With Chronic Heart Failure Circulation, January 25, 2005; 111(3): 310 - 314. [Abstract] [Full Text] [PDF]
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