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Published in: Basic Research in Cardiology 3/2008

01-05-2008 | ORIGINAL CONTRIBUTION

Age-dependent endothelial dysfunction is associated with failure to increase plasma nitrite in response to exercise

Authors: Thomas Lauer, MD, Christian Heiss, MD, Jan Balzer, MD, Eva Kehmeier, MD, Sarah Mangold, MD, Thorsten Leyendecker, MD, Jessica Rottler, MD, Christian Meyer, MD, Marc W. Merx, MD, Malte Kelm, MD, FESC, Tienush Rassaf, MD

Published in: Basic Research in Cardiology | Issue 3/2008

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Abstract

Age-dependent alterations of the vessel wall may predispose older individuals to increased cardiovascular pathology. Aging is associated with an impaired bioactivity of nitric oxide (NO). Plasma nitrite reflects NO-synthase activity under fasting conditions and is an important storage pool of NO. To test the hypothesis that aging is associated with an impaired capacity of the vasculature to increase plasma nitrite during exercise, 29 young and 28 old healthy individuals (25 ± 1 years and 58 ± 2 years; P < 0.001) without major cardiovascular risk factors were enrolled. Exercise stress was similar in both groups. Baseline nitrite did not differ (107 ± 8 vs. 82 ± 10 nmol/l, young vs. old; n.s.) although a trend toward higher nitrite levels in young individuals was seen. In young subjects, exercise increased plasma nitrite by 38 ± 7% (P < 0.001) compared to only 13 ± 8% (P = n.s.) in older subjects. L-NMMA blocked increases of nitrite. Endothelial function, as defined by flow–mediated-dilation (FMD) of the brachial artery via ultrasound, was impaired in older subjects (5.4 ± 0.4% vs. 6.7 ± 0.3%; P < 0.01). Multivariate analysis showed that age (P = 0.007), BMI (P = 0.010), and LDL (P = 0.021) were independent predictors of nitrite increase. The fact that aging is associated with an impaired capacity of the vasculature to adequately increase nitrite to physiological stimuli may contribute to attenuated maintenance and further deterioration of vascular homeostasis with aging.
Literature
1.
go back to reference Adult Treatment Panel III (2001) Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. JAMA 285:2486–2497 Adult Treatment Panel III (2001) Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. JAMA 285:2486–2497
2.
go back to reference Benjamin N, O’Driscoll F, Dougall H, Duncan C, Smith L, Golden M, McKenzie H (1994) Stomach NO synthesis. Nature 368:502PubMedCrossRef Benjamin N, O’Driscoll F, Dougall H, Duncan C, Smith L, Golden M, McKenzie H (1994) Stomach NO synthesis. Nature 368:502PubMedCrossRef
3.
go back to reference Bryan NS, Fernandez BO, Bauer SM, Garcia-Saura MF, Milsom AB, Rassaf T, Maloney RE, Bharti A, Rodriguez J, Feelisch M (2005) Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol 1:290–297PubMedCrossRef Bryan NS, Fernandez BO, Bauer SM, Garcia-Saura MF, Milsom AB, Rassaf T, Maloney RE, Bharti A, Rodriguez J, Feelisch M (2005) Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol 1:290–297PubMedCrossRef
4.
go back to reference Bryan NS, Rassaf T, Maloney RE, Rodriguez CM, Saijo F, Rodriguez JR, Feelisch M (2004) Cellular targets and mechanisms of nitros(yl)ation: An insight into their nature and kinetics in vivo. Proc Natl Acad Sci USA 101:4308–4313PubMedCrossRef Bryan NS, Rassaf T, Maloney RE, Rodriguez CM, Saijo F, Rodriguez JR, Feelisch M (2004) Cellular targets and mechanisms of nitros(yl)ation: An insight into their nature and kinetics in vivo. Proc Natl Acad Sci USA 101:4308–4313PubMedCrossRef
5.
go back to reference Castelli WP (1984) Epidemiology of coronary heart disease: the Framingham study. Am J Med 76:4–12PubMedCrossRef Castelli WP (1984) Epidemiology of coronary heart disease: the Framingham study. Am J Med 76:4–12PubMedCrossRef
6.
go back to reference Chen X, Niroomand F, Liu Z, Zankl A, Katus HA, Jahn L, Tiefenbacher CP (2006) Expression of nitric oxide related enzymes in coronary heart disease. Basic Res Cardiol 101:346–353PubMedCrossRef Chen X, Niroomand F, Liu Z, Zankl A, Katus HA, Jahn L, Tiefenbacher CP (2006) Expression of nitric oxide related enzymes in coronary heart disease. Basic Res Cardiol 101:346–353PubMedCrossRef
7.
go back to reference Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ (2003) Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of hight blood pressure. Hypertension 42:1206–1252PubMedCrossRef Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Roccella EJ (2003) Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of hight blood pressure. Hypertension 42:1206–1252PubMedCrossRef
8.
go back to reference Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, Yang BK, Waclawiw MA, Zalos G, Xu X, Huang KT, Shields H, Kim-Shapiro DB, Schechter AN, Cannon III RO, Gladwin MT (2003) Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med 9:1498–1505PubMedCrossRef Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, Yang BK, Waclawiw MA, Zalos G, Xu X, Huang KT, Shields H, Kim-Shapiro DB, Schechter AN, Cannon III RO, Gladwin MT (2003) Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med 9:1498–1505PubMedCrossRef
9.
go back to reference Crawford JH, Isbell TS, Huang Z, Shiva S, Chacko BK, Schechter AN, Darley-Usmar VM, Kerby JD, Lang JD Jr., Kraus D, Ho C, Gladwin MT, Patel RP (2006) Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation. Blood 107:566–574PubMedCrossRef Crawford JH, Isbell TS, Huang Z, Shiva S, Chacko BK, Schechter AN, Darley-Usmar VM, Kerby JD, Lang JD Jr., Kraus D, Ho C, Gladwin MT, Patel RP (2006) Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation. Blood 107:566–574PubMedCrossRef
10.
go back to reference Donato AJ, Eskurza I, Silver AE, Levy AS, Pierce GL, Gates PE, Seals DR (2007) Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-kappaB. Circ Res 100:1659–1666PubMedCrossRef Donato AJ, Eskurza I, Silver AE, Levy AS, Pierce GL, Gates PE, Seals DR (2007) Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-kappaB. Circ Res 100:1659–1666PubMedCrossRef
11.
go back to reference Doyle MP, Pickering RA, DeWeert TM, Hoekstra JW, Pater D (1981) Kinetics and mechanism of the oxidation of human deoxyhemoglobin by nitrites. J Biol Chem 256:12393–12398PubMed Doyle MP, Pickering RA, DeWeert TM, Hoekstra JW, Pater D (1981) Kinetics and mechanism of the oxidation of human deoxyhemoglobin by nitrites. J Biol Chem 256:12393–12398PubMed
12.
go back to reference Duranski MR, Greer JJ, Dejam A, Jaganmohan S, Hogg N, Langston W, Patel RP, Yet SF, Wang X, Kevil CG, Gladwin MT, Lefer DJ (2005) Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver. J Clin Invest 115:1232–1240PubMed Duranski MR, Greer JJ, Dejam A, Jaganmohan S, Hogg N, Langston W, Patel RP, Yet SF, Wang X, Kevil CG, Gladwin MT, Lefer DJ (2005) Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver. J Clin Invest 115:1232–1240PubMed
13.
go back to reference Finkel T (2005) Opinion: Radical medicine: treating ageing to cure disease. Nat Rev Mol Cell Biol 6:971–976PubMedCrossRef Finkel T (2005) Opinion: Radical medicine: treating ageing to cure disease. Nat Rev Mol Cell Biol 6:971–976PubMedCrossRef
14.
go back to reference Fisher ND, Hollenberg NK (2006) Aging and vascular responses to flavanol-rich cocoa. J Hypertens 24:1575–1580PubMedCrossRef Fisher ND, Hollenberg NK (2006) Aging and vascular responses to flavanol-rich cocoa. J Hypertens 24:1575–1580PubMedCrossRef
15.
go back to reference Gibbons RJ, Balady GJ, Beasley JW, Bricker JT, Duvernoy WF, Froelicher VF, Mark DB, Marwick TH, McCallister BD, Thompson PD Jr., Winters WL, Yanowitz FG, Ritchie JL, Gibbons RJ, Cheitlin MD, Eagle KA, Gardner TJ, Garson A Jr., Lewis RP, O’Rourke RA, Ryan TJ (1997) ACC/AHA guidelines for exercise testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). J Am Coll Cardiol 30:260–311PubMedCrossRef Gibbons RJ, Balady GJ, Beasley JW, Bricker JT, Duvernoy WF, Froelicher VF, Mark DB, Marwick TH, McCallister BD, Thompson PD Jr., Winters WL, Yanowitz FG, Ritchie JL, Gibbons RJ, Cheitlin MD, Eagle KA, Gardner TJ, Garson A Jr., Lewis RP, O’Rourke RA, Ryan TJ (1997) ACC/AHA guidelines for exercise testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). J Am Coll Cardiol 30:260–311PubMedCrossRef
16.
go back to reference Gladwin MT, Schechter AN, Kim-Shapiro DB, Patel R, Hogg N, Shiva S, Cannon III RO, Kelm M, Wink D, Espey MG, Oldfield E, Pluta RM, Freeman BA, Lancaster Jr. JR, Feelisch M, Lundberg JO (2005) The emerging role of nitrite. Nat Chem Biol 1:308–314PubMedCrossRef Gladwin MT, Schechter AN, Kim-Shapiro DB, Patel R, Hogg N, Shiva S, Cannon III RO, Kelm M, Wink D, Espey MG, Oldfield E, Pluta RM, Freeman BA, Lancaster Jr. JR, Feelisch M, Lundberg JO (2005) The emerging role of nitrite. Nat Chem Biol 1:308–314PubMedCrossRef
17.
go back to reference Hamilton CA, Brosnan MJ, McIntyre M, Graham D, Dominiczak AF (2001) Superoxide excess in hypertension and aging: a common cause of endothelial dysfunction. Hypertension 37:529–534PubMed Hamilton CA, Brosnan MJ, McIntyre M, Graham D, Dominiczak AF (2001) Superoxide excess in hypertension and aging: a common cause of endothelial dysfunction. Hypertension 37:529–534PubMed
18.
go back to reference Huang X, Yang P, Du Y, Zhang J, Ma A (2007) Age-related down-regulation of HCN channels in rat sinoatrial node. Basic Res Cardiol 102:429–435PubMedCrossRef Huang X, Yang P, Du Y, Zhang J, Ma A (2007) Age-related down-regulation of HCN channels in rat sinoatrial node. Basic Res Cardiol 102:429–435PubMedCrossRef
19.
go back to reference Kleinbongard P, Dejam A, Lauer T, Jax T, Kerber S, Gharini P, Balzer J, Zotz RB, Scharf RE, Willers R, Schechter AN, Feelisch M, Kelm M (2006) Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans. Free Radic Biol Med 40:295–302PubMedCrossRef Kleinbongard P, Dejam A, Lauer T, Jax T, Kerber S, Gharini P, Balzer J, Zotz RB, Scharf RE, Willers R, Schechter AN, Feelisch M, Kelm M (2006) Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans. Free Radic Biol Med 40:295–302PubMedCrossRef
20.
go back to reference Kleinbongard P, Dejam A, Lauer T, Rassaf T, Schindler A, Picker O, Scheeren T, Godecke A, Schrader J, Schulz R, Heusch G, Schaub GA, Bryan NS, Feelisch M, Kelm M (2003) Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals. Free Radic Biol Med 35:790–796PubMedCrossRef Kleinbongard P, Dejam A, Lauer T, Rassaf T, Schindler A, Picker O, Scheeren T, Godecke A, Schrader J, Schulz R, Heusch G, Schaub GA, Bryan NS, Feelisch M, Kelm M (2003) Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals. Free Radic Biol Med 35:790–796PubMedCrossRef
21.
go back to reference Lauer T, Kleinbongard P, Preik M, Rauch BH, Deussen A, Feelisch M, Strauer BE, Kelm M (2003) Direct biochemical evidence for eNOS stimulation by bradykinin in the human forearm vasculature. Basic Res Cardiol 98:84–89PubMedCrossRef Lauer T, Kleinbongard P, Preik M, Rauch BH, Deussen A, Feelisch M, Strauer BE, Kelm M (2003) Direct biochemical evidence for eNOS stimulation by bradykinin in the human forearm vasculature. Basic Res Cardiol 98:84–89PubMedCrossRef
22.
go back to reference Lauer T, Preik M, Rassaf T, Strauer BE, Deussen A, Feelisch M, Kelm M (2001) Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action. Proc Natl Acad Sci USA 98:12814–12819PubMedCrossRef Lauer T, Preik M, Rassaf T, Strauer BE, Deussen A, Feelisch M, Kelm M (2001) Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action. Proc Natl Acad Sci USA 98:12814–12819PubMedCrossRef
24.
go back to reference Lundberg JO, Govoni M (2004) Inorganic nitrate is a possible source for systemic generation of nitric oxide. Free Radic Biol Med 37:395–400PubMedCrossRef Lundberg JO, Govoni M (2004) Inorganic nitrate is a possible source for systemic generation of nitric oxide. Free Radic Biol Med 37:395–400PubMedCrossRef
25.
go back to reference Lundberg JO, Weitzberg E, Lundberg JM, Alving K (1994) Intragastric nitric oxide production in humans: measurements in expelled air. Gut 35:1543–1546PubMedCrossRef Lundberg JO, Weitzberg E, Lundberg JM, Alving K (1994) Intragastric nitric oxide production in humans: measurements in expelled air. Gut 35:1543–1546PubMedCrossRef
26.
go back to reference Mujynya-Ludunge K, Viswambharan H, Driscoll R, Ming XF, von Segesser LK, Kappenberger L, Yang Z, Vassalli G (2005) Endothelial nitric oxide synthase gene transfer restores endothelium-dependent relaxations and attenuates lesion formation in carotid arteries in apolipoprotein E-deficient mice. Basic Res Cardiol 100:102–111PubMedCrossRef Mujynya-Ludunge K, Viswambharan H, Driscoll R, Ming XF, von Segesser LK, Kappenberger L, Yang Z, Vassalli G (2005) Endothelial nitric oxide synthase gene transfer restores endothelium-dependent relaxations and attenuates lesion formation in carotid arteries in apolipoprotein E-deficient mice. Basic Res Cardiol 100:102–111PubMedCrossRef
28.
go back to reference Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, Greenland P, Grundy SM, Hong Y, Miller NH, Lauer RM, Ockene IS, Sacco RL, Sallis JF Jr., Smith SC Jr., Stone NJ, Taubert KA (2002) AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation 106:388–391PubMedCrossRef Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, Greenland P, Grundy SM, Hong Y, Miller NH, Lauer RM, Ockene IS, Sacco RL, Sallis JF Jr., Smith SC Jr., Stone NJ, Taubert KA (2002) AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation 106:388–391PubMedCrossRef
29.
go back to reference Penna C, Cappello S, Mancardi D, Raimondo S, Rastaldo R, Gattullo D, Losano G, Pagliaro P (2006) Post-conditioning reduces infarct size in the isolated rat heart: role of coronary flow and pressure and the nitric oxide/cGMP pathway. Basic Res Cardiol 101:168–179PubMedCrossRef Penna C, Cappello S, Mancardi D, Raimondo S, Rastaldo R, Gattullo D, Losano G, Pagliaro P (2006) Post-conditioning reduces infarct size in the isolated rat heart: role of coronary flow and pressure and the nitric oxide/cGMP pathway. Basic Res Cardiol 101:168–179PubMedCrossRef
30.
go back to reference Rassaf T, Feelisch M, Kelm M (2004) Circulating NO pool: assessment of nitrite and nitroso species in blood and tissues. Free Radic Biol Med 36:413–422PubMedCrossRef Rassaf T, Feelisch M, Kelm M (2004) Circulating NO pool: assessment of nitrite and nitroso species in blood and tissues. Free Radic Biol Med 36:413–422PubMedCrossRef
31.
go back to reference Rassaf T, Flogel U, Drexhage C, Hendgen-Cotta U, Kelm M, Schrader J (2007) Nitrite reductase function of deoxymyoglobin: oxygen sensor and regulator of cardiac energetics and function. Circ Res 100:1749–1754PubMedCrossRef Rassaf T, Flogel U, Drexhage C, Hendgen-Cotta U, Kelm M, Schrader J (2007) Nitrite reductase function of deoxymyoglobin: oxygen sensor and regulator of cardiac energetics and function. Circ Res 100:1749–1754PubMedCrossRef
32.
go back to reference Rassaf T, Heiss C, Hendgen-Cotta U, Balzer J, Matern S, Kleinbongard P, Lee A, Lauer T, Kelm M (2006) Plasma nitrite reserve and endothelial function in the human forearm circulation. Free Radic Biol Med 41:295–301PubMedCrossRef Rassaf T, Heiss C, Hendgen-Cotta U, Balzer J, Matern S, Kleinbongard P, Lee A, Lauer T, Kelm M (2006) Plasma nitrite reserve and endothelial function in the human forearm circulation. Free Radic Biol Med 41:295–301PubMedCrossRef
33.
go back to reference Rassaf T, Kleinbongard P, Preik M, Dejam A, Gharini P, Lauer T, Erckenbrecht J, Duschin A, Schulz R, Heusch G, Feelisch M, Kelm M (2002) Plasma nitrosothiols contribute to the systemic vasodilator effects of intravenously applied NO: Experimental and clinical study on the fate of NO in human blood. Circ Res 91:470–477PubMedCrossRef Rassaf T, Kleinbongard P, Preik M, Dejam A, Gharini P, Lauer T, Erckenbrecht J, Duschin A, Schulz R, Heusch G, Feelisch M, Kelm M (2002) Plasma nitrosothiols contribute to the systemic vasodilator effects of intravenously applied NO: Experimental and clinical study on the fate of NO in human blood. Circ Res 91:470–477PubMedCrossRef
34.
go back to reference Rassaf T, Lauer T, Heiss C, Balzer J, Mangold S, Leyendecker T, Rottler J, Drexhage C, Meyer C, Kelm M (2007) Nitric oxide synthase derived plasma nitrite predicts exercise capacity. Br J Sports Med 41:669–673PubMedCrossRef Rassaf T, Lauer T, Heiss C, Balzer J, Mangold S, Leyendecker T, Rottler J, Drexhage C, Meyer C, Kelm M (2007) Nitric oxide synthase derived plasma nitrite predicts exercise capacity. Br J Sports Med 41:669–673PubMedCrossRef
35.
go back to reference Rassaf T, Poll LW, Brouzos P, Lauer T, Totzeck M, Kleinbongard P, Gharini P, Andersen K, Schulz R, Heusch G, Modder U, Kelm M (2006) Positive effects of nitric oxide on left ventricular function in humans. Eur Heart J 27:1699–1705PubMedCrossRef Rassaf T, Poll LW, Brouzos P, Lauer T, Totzeck M, Kleinbongard P, Gharini P, Andersen K, Schulz R, Heusch G, Modder U, Kelm M (2006) Positive effects of nitric oxide on left ventricular function in humans. Eur Heart J 27:1699–1705PubMedCrossRef
36.
go back to reference Rassaf T, Preik M, Kleinbongard P, Lauer T, Heiß C, Strauer BE, Feelisch M, Kelm M (2002) Evidence for in vivo transport of bioactive nitric oxide in human plasma. J Clin Invest 109:1241–1248PubMed Rassaf T, Preik M, Kleinbongard P, Lauer T, Heiß C, Strauer BE, Feelisch M, Kelm M (2002) Evidence for in vivo transport of bioactive nitric oxide in human plasma. J Clin Invest 109:1241–1248PubMed
37.
go back to reference Shiva S, Huang Z, Grubina R, Sun J, Ringwood LA, Macarthur PH, Xu X, Murphy E, Darley-Usmar VM, Gladwin MT (2007) Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration. Circ Res Shiva S, Huang Z, Grubina R, Sun J, Ringwood LA, Macarthur PH, Xu X, Murphy E, Darley-Usmar VM, Gladwin MT (2007) Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration. Circ Res
38.
go back to reference Shiva S, Wang X, Ringwood LA, Xu X, Yuditskaya S, Annavajjhala V, Miyajima H, Hogg N, Harris ZL, Gladwin MT (2006) Ceruloplasmin is a NO oxidase and nitrite synthase that determines endocrine NO homeostasis. Nat Chem Biol 2:486–493PubMedCrossRef Shiva S, Wang X, Ringwood LA, Xu X, Yuditskaya S, Annavajjhala V, Miyajima H, Hogg N, Harris ZL, Gladwin MT (2006) Ceruloplasmin is a NO oxidase and nitrite synthase that determines endocrine NO homeostasis. Nat Chem Biol 2:486–493PubMedCrossRef
39.
go back to reference Tanner FC, van der LB, Shaw S, Greutert H, Bachschmid MM, Berrozpe M, Rozenberg I, Blau N, Siebenmann R, Schmidli J, Meyer P, Luscher TF (2007) Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery. Basic Res Cardiol 102:308–317 Tanner FC, van der LB, Shaw S, Greutert H, Bachschmid MM, Berrozpe M, Rozenberg I, Blau N, Siebenmann R, Schmidli J, Meyer P, Luscher TF (2007) Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery. Basic Res Cardiol 102:308–317
40.
go back to reference Turcato S, Turnbull L, Wang GY, Honbo N, Simpson PC, Karliner JS, Baker AJ (2006) Ischemic preconditioning depends on age and gender. Basic Res Cardiol 101:235–243PubMedCrossRef Turcato S, Turnbull L, Wang GY, Honbo N, Simpson PC, Karliner JS, Baker AJ (2006) Ischemic preconditioning depends on age and gender. Basic Res Cardiol 101:235–243PubMedCrossRef
41.
go back to reference Webb A, Bond R, McLean P, Uppal R, Benjamin N, Ahluwalia A (2004) Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Proc Natl Acad Sci USA 101:13683–13688PubMedCrossRef Webb A, Bond R, McLean P, Uppal R, Benjamin N, Ahluwalia A (2004) Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Proc Natl Acad Sci USA 101:13683–13688PubMedCrossRef
42.
go back to reference Weinsaft JW, Edelberg JM (2001) Aging-associated changes in vascular activity: a potential link to geriatric cardiovascular disease. Am J Geriatr Cardiol 10:348–354PubMedCrossRef Weinsaft JW, Edelberg JM (2001) Aging-associated changes in vascular activity: a potential link to geriatric cardiovascular disease. Am J Geriatr Cardiol 10:348–354PubMedCrossRef
43.
go back to reference Zweier JL, Wang P, Samouilov A, Kuppusamy P (1995) Enzyme-independent formation of nitric oxide in biological tissues. Nat Med 1:804–809PubMedCrossRef Zweier JL, Wang P, Samouilov A, Kuppusamy P (1995) Enzyme-independent formation of nitric oxide in biological tissues. Nat Med 1:804–809PubMedCrossRef
Metadata
Title
Age-dependent endothelial dysfunction is associated with failure to increase plasma nitrite in response to exercise
Authors
Thomas Lauer, MD
Christian Heiss, MD
Jan Balzer, MD
Eva Kehmeier, MD
Sarah Mangold, MD
Thorsten Leyendecker, MD
Jessica Rottler, MD
Christian Meyer, MD
Marc W. Merx, MD
Malte Kelm, MD, FESC
Tienush Rassaf, MD
Publication date
01-05-2008
Publisher
D. Steinkopff-Verlag
Published in
Basic Research in Cardiology / Issue 3/2008
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI
https://doi.org/10.1007/s00395-008-0714-3

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