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(Hypertension. 1996;27:849-853.)
© 1996 American Heart Association, Inc.
Articles |
Aging Progressively Impairs Endothelium-Dependent Vasodilation in Forearm Resistance Vessels of Humans
From the Vascular Medicine and Atherosclerosis Unit of the Cardiovascular Division, Brigham and Women's Hospital, and Harvard Medical School, Boston, Mass.
Abstract Studies in experimental models suggest that endothelium-derived nitric oxide is reduced with aging, and this circumstance may be relevant to atherogenesis. The aim of this study was to determine whether increasing age resulted in altered endothelium-dependent vasodilation in the forearm resistance vessels of healthy humans. Forearm blood flow was measured in 119 healthy subjects, aged 19 to 69 years, by venous occlusion plethysmography. Brachial artery infusions of methacholine chloride (0.03 to 10.0 µg/min) were used to assess endothelium-dependent vasodilation and of sodium nitroprusside (0.03 to 10.0 µg/min) to assess endothelium-independent vasodilation. The slope of the dose–blood flow response relation was calculated in each subject for each drug. Univariate and multiple stepwise regression analyses were used to relate vascular reactivity to selected variables, including age, lipids, and blood pressure. Endothelium-dependent vasodilation was progressively impaired with increasing age, assessed as a reduction in slope from 2.25±0.16 to 0.34±0.11 (mL/100 mL tissue per minute)/(µg/min) (P<.001). The decline in endothelium-dependent vasodilation was already evident by the fourth decade (age 30 to 39 years). Endothelium-independent vasodilation did not change with age. Age, total cholesterol, and low-density lipoprotein cholesterol were univariate predictors of endothelium-dependent vasodilation. Age remained the most significant predictor of endothelium-dependent vasodilator responses by multiple stepwise regression analysis. From these observations, it can be concluded that endothelium-dependent vasodilation declines steadily with increasing age in healthy human subjects. Age is a strong univariate and multivariate predictor of endothelium-dependent vasodilation. This finding may be a marker for more widespread endothelial dysfunction.
Key Words: aging • vasodilation • nitric oxide • atherosclerosis
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 F. Khan, S. J Litchfield, P. A Stonebridge, and J. J. Belch Lipid-lowering and skin vascular responses in patients with hypercholesterolaemia and peripheral arterial obstructive disease Vascular Medicine, November 1, 1999; 4(4): 233 - 238. [Abstract] [PDF]
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J. Case and C. A. Davison Estrogen Alters Relative Contributions of Nitric Oxide and Cyclooxygenase Products to Endothelium-Dependent Vasodilation J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 524 - 530. [Abstract] [Full Text]
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S. J Duffy, G. New, R. W Harper, and I. T Meredith Metabolic vasodilation in the human forearm is preserved in hypercholesterolemia despite impairment of endothelium-dependent and independent vasodilation Cardiovasc Res, August 15, 1999; 43(3): 721 - 730. [Abstract] [Full Text] [PDF]
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G. E. McVeigh, C. W. Bratteli, D. J. Morgan, C. M. Alinder, S. P. Glasser, S. M. Finkelstein, and J. N. Cohn Age-Related Abnormalities in Arterial Compliance Identified by Pressure Pulse Contour Analysis : Aging and Arterial Compliance Hypertension, June 1, 1999; 33(6): 1392 - 1398. [Abstract] [Full Text] [PDF]
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G. Dell'Omo, L. Ferrini, M. Morale, F. De Negri, E. Melillo, F. Carmassi, and R. Pedrinelli Acetylcholine-Mediated Vasodilatation and Tissue-type Plasminogen Activator Release in Normal and Hypertensive Men Angiology, April 1, 1999; 50(4): 273 - 282. [Abstract] [PDF]
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M. Kahonen, K. Karjala, N. Hutri-Kahonen, X. Wu, P. Jaatinen, P. Riihioja, A. Hervonen, and I. Porsti Influence of chronic ethanol consumption on arterial tone in young and aged rats Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H464 - H471. [Abstract] [Full Text] [PDF]
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A. Rivard, J.-E. Fabre, M. Silver, D. Chen, T. Murohara, M. Kearney, M. Magner, T. Asahara, and J. M. Isner Age-Dependent Impairment of Angiogenesis Circulation, January 12, 1999; 99(1): 111 - 120. [Abstract] [Full Text] [PDF]
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M. D. Delp, M. V. Evans, and C. Duan Effects of aging on cardiac output, regional blood flow, and body composition in Fischer-344 rats J Appl Physiol, November 1, 1998; 85(5): 1813 - 1822. [Abstract] [Full Text] [PDF]
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 M. R. Cernadas, L. S. de Miguel, M. Garcia-Duran, F. Gonzalez-Fernandez, I. Millas, M. Monton, J. Rodrigo, L. Rico, P. Fernandez, T. de Frutos, et al. Expression of Constitutive and Inducible Nitric Oxide Synthases in the Vascular Wall of Young and Aging Rats Circ. Res., August 10, 1998; 83(3): 279 - 286. [Abstract] [Full Text] [PDF]
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R. V. Hogikyan, A. T. Galecki, B. Pitt, J. B. Halter, D. A. Greene, and M. A. Supiano Specific Impairment of Endothelium-Dependent Vasodilation in Subjects with Type 2 Diabetes Independent of Obesity J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 1946 - 1952. [Abstract] [Full Text]
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 F. M. FARACI and D. D. HEISTAD Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels Physiol Rev, January 1, 1998; 78(1): 53 - 97. [Abstract] [Full Text] [PDF]
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M. Hausberg, R. P. Hoffman, V. K. Somers, C. A. Sinkey, A. L. Mark, and E. A. Anderson Contrasting Autonomic and Hemodynamic Effects of Insulin in Healthy Elderly Versus Young Subjects Hypertension, March 1, 1997; 29(3): 700 - 705. [Abstract] [Full Text]
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S. Taddei, A. Virdis, P. Mattei, L. Ghiadoni, C. B. Fasolo, I. Sudano, and A. Salvetti Hypertension Causes Premature Aging of Endothelial Function in Humans Hypertension, March 1, 1997; 29(3): 736 - 743. [Abstract] [Full Text]
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E. D. Frohlich Influence of Nitric Oxide and Angiotensin II on Renal Involvement in Hypertension Hypertension, January 1, 1997; 29(1): 188 - 193. [Abstract] [Full Text] [PDF]
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S. Pinto, A. Virdis, L. Ghiadoni, G. Bernini, M. Lombardo, F. Petraglia, A. R. Genazzani, S. Taddei, and A. Salvetti Endogenous Estrogen and Acetylcholine-Induced Vasodilation in Normotensive Women Hypertension, January 1, 1997; 29(1): 268 - 273. [Abstract] [Full Text] [PDF]
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 C. Kalka, H. Masuda, T. Takahashi, W. M. Kalka-Moll, M. Silver, M. Kearney, T. Li, J. M. Isner, and T. Asahara Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization PNAS, March 28, 2000; 97(7): 3422 - 3427. [Abstract] [Full Text] [PDF]
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H. Iwaguro, J.-i. Yamaguchi, C. Kalka, S. Murasawa, H. Masuda, S.-i. Hayashi, M. Silver, T. Li, J. M. Isner, and T. Asahara Endothelial Progenitor Cell Vascular Endothelial Growth Factor Gene Transfer for Vascular Regeneration Circulation, February 12, 2002; 105(6): 732 - 738. [Abstract] [Full Text] [PDF]
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