Circulation, Vol 88, 2510-2516, Copyright © 1993 by American Heart Association
MT Johnstone, SJ Creager, KM Scales, JA Cusco, BK Lee and MA Creager
BACKGROUND. Endothelium-dependent vasodilation is abnormal in experimental
models of diabetes mellitus. We postulated that abnormalities of
endothelial function are also present in patients with insulin-dependent
diabetes mellitus and may contribute to the pathogenesis of vascular
disease in these individuals. METHODS AND RESULTS. Vascular reactivity was
measured in the forearm resistance vessels of 15 patients with
insulin-dependent diabetes mellitus and 16 age-matched normal subjects. No
patient had hypertension or dyslipidemia. Each subject was pretreated with
aspirin to inhibit endogenous production of prostanoids. Methacholine
chloride (0.3 to 10 micrograms/min) was administered via the brachial
artery to assess endothelium-dependent vasodilation. Sodium nitroprusside
(0.3 to 10 micrograms/min) and verapamil (10 to 300 micrograms/min) were
infused intra-arterially to assess endothelium-independent vasodilation;
phenylephrine (0.3 to 3 micrograms/min) was administered to examine
vasoconstrictor responsiveness. Forearm blood flow was determined by venous
occlusion plethysmography, and dose-response curves were generated for each
drug. Basal forearm blood flow in diabetic and normal subjects was
comparable (2.6 +/- 0.2 versus 2.1 +/- 0.3 mL x 100 mL-1 x min-1,
respectively; P = NS). The forearm vasodilative response to methacholine
was less in diabetic than in normal subjects. At the highest dose of
methacholine, the forearm blood flow increased 9.5 +/- 1.1 mL x 100 mL-1 x
min-1 in diabetic subjects and 15.3 +/- 1.4 mL.100 mL-1 x min-1 in normal
subjects (P < .01). The forearm blood flow responses to nitroprusside
and verapamil and the forearm vasoconstrictor responses to phenylephrine
were similar in diabetic and healthy subjects. In diabetic subjects,
endothelium-dependent vasodilation correlated inversely with serum insulin
concentration but not with glucose concentration, glycosylated hemoglobin,
or duration of diabetes. CONCLUSIONS. Endothelium-dependent vasodilation is
abnormal in forearm resistance vessels of patients with insulin-dependent
diabetes mellitus. This abnormality may be relevant to the high prevalence
of vascular disease that occurs in these individuals.
ARTICLES
Impaired endothelium-dependent vasodilation in patients with insulin- dependent diabetes mellitus
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115.
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L. Schwartz, K. E. Kip, R. L. Frye, E. L. Alderman, H. V. Schaff, and K. M. Detre Coronary Bypass Graft Patency in Patients With Diabetes in the Bypass Angioplasty Revascularization Investigation (BARI) Circulation, November 19, 2002; 106(21): 2652 - 2658. [Abstract] [Full Text] [PDF]
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 K. J. Stewart Exercise Training and the Cardiovascular Consequences of Type 2 Diabetes and Hypertension: Plausible Mechanisms for Improving Cardiovascular Health JAMA, October 2, 2002; 288(13): 1622 - 1631. [Abstract] [Full Text] [PDF]
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A. Hansen, B.-L. Johansson, J. Wahren, and H. von Bibra C-Peptide Exerts Beneficial Effects on Myocardial Blood Flow and Function in Patients With Type 1 Diabetes Diabetes, October 1, 2002; 51(10): 3077 - 3082. [Abstract] [Full Text] [PDF]
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M. G. Modena, L. Bonetti, F. Coppi, F. Bursi, and R. Rossi Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women J. Am. Coll. Cardiol., August 7, 2002; 40(3): 505 - 510. [Abstract] [Full Text] [PDF]
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C. Desouza, A. Parulkar, D. Lumpkin, D. Akers, and V. A. Fonseca Acute and Prolonged Effects of Sildenafil on Brachial Artery Flow-Mediated Dilatation in Type 2 Diabetes Diabetes Care, August 1, 2002; 25(8): 1336 - 1339. [Abstract] [Full Text] [PDF]
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J. A. Beckman, M. A. Creager, and P. Libby Diabetes and Atherosclerosis: Epidemiology, Pathophysiology, and Management JAMA, May 15, 2002; 287(19): 2570 - 2581. [Abstract] [Full Text] [PDF]
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T. Maeno, H. Koyama, H. Tahara, M. Komatsu, M. Emoto, T. Shoji, M. Inaba, T. Miki, Y. Okuno, and Y. Nishizawa The 807T Allele in {alpha}2 Integrin Is Protective Against Atherosclerotic Arterial Wall Thickening and the Occurrence of Plaque in Patients With Type 2 Diabetes Diabetes, May 1, 2002; 51(5): 1523 - 1528. [Abstract] [Full Text] [PDF]
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F. H. Epstein, A. Veves, and P. V. Prasad Effect of Diabetes on Renal Medullary Oxygenation During Water Diuresis Diabetes Care, March 1, 2002; 25(3): 575 - 578. [Abstract] [Full Text] [PDF]
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A. Nitenberg, S. Ledoux, P. Valensi, R. Sachs, and I. Antony Coronary Microvascular Adaptation to Myocardial Metabolic Demand Can Be Restored by Inhibition of Iron-Catalyzed Formation of Oxygen Free Radicals in Type 2 Diabetic Patients Diabetes, March 1, 2002; 51(3): 813 - 818. [Abstract] [Full Text] [PDF]
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K. C. B. Tan, W. S. Chow, S. C. F. Tam, V. H. G. Ai, C. H. L. Lam, and K. S. L. Lam Atorvastatin Lowers C-Reactive Protein and Improves Endothelium-Dependent Vasodilation in Type 2 Diabetes Mellitus J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 563 - 568. [Abstract] [Full Text] [PDF]
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Y. K. Kim, M.-S. Lee, S. M. Son, I. J. Kim, W. S. Lee, B. Y. Rhim, K. W. Hong, and C. D. Kim Vascular NADH Oxidase Is Involved in Impaired Endothelium-Dependent Vasodilation in OLETF Rats, a Model of Type 2 Diabetes Diabetes, February 1, 2002; 51(2): 522 - 527. [Abstract] [Full Text] [PDF]
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D. Hurlimann, F. Ruschitzka, and T.F. Luscher The relationship between the endothelium and the vessel wall Eur. Heart J. Suppl., February 1, 2002; 4(suppl_A): A1 - A7. [Abstract] [PDF]
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K. J. Zuzak, M. D. Schaeberle, M. T. Gladwin, R. O. Cannon III, and I. W. Levin Noninvasive Determination of Spatially Resolved and Time-Resolved Tissue Perfusion in Humans During Nitric Oxide Inhibition and Inhalation by Use of a Visible-Reflectance Hyperspectral Imaging Technique Circulation, December 11, 2001; 104(24): 2905 - 2910. [Abstract] [Full Text] [PDF]
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M. J. Joyner, N. M. Dietz, and J. T. Shepherd From Belfast to Mayo and beyond: the use and future of plethysmography to study blood flow in human limbs J Appl Physiol, December 1, 2001; 91(6): 2431 - 2441. [Abstract] [Full Text] [PDF]
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C. H. Pullin, P. A. L. Ashfield-Watt, M. L. Burr, Z. E. Clark, M. J. Lewis, S. J. Moat, R. G. Newcombe, H. J. Powers, J. M. Whiting, and I. F. W. McDowell Optimization of dietary folate or low-dose folic acid supplements lower homocysteine but do not enhance endothelial function in healthy adults, irrespective of the methylenetetrahydrofolate reductase (C677T) genotype J. Am. Coll. Cardiol., December 1, 2001; 38(7): 1799 - 1805. [Abstract] [Full Text] [PDF]
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J. S. Romney and R. Z. Lewanczuk Vascular Compliance Is Reduced in the Early Stages of Type 1 Diabetes Diabetes Care, December 1, 2001; 24(12): 2102 - 2106. [Abstract] [Full Text] [PDF]
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M. Annuk, M. Zilmer, L. Lind, T. Linde, and B. Fellstrom Oxidative Stress and Endothelial Function in Chronic Renal Failure J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2747 - 2752. [Abstract] [Full Text] [PDF]
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 F. A Van Assche, K. Holemans, and L. Aerts Long-term consequences for offspring of diabetes during pregnancy Br. Med. Bull., November 1, 2001; 60(1): 173 - 182. [Abstract] [Full Text] [PDF]
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M. A van de Ree, M. V Huisman, F. H de Man, J. C van der Vijver, A.E. Meinders, and G. J Blauw Impaired endothelium-dependent vasodilation in type 2 diabetes mellitus and the lack of effect of simvastatin Cardiovasc Res, November 1, 2001; 52(2): 299 - 305. [Abstract] [Full Text] [PDF]
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M. Imamura, S. Biro, T. Kihara, S. Yoshifuku, K. Takasaki, Y. Otsuji, S. Minagoe, Y. Toyama, and C. Tei Repeated thermal therapy improves impaired vascular endothelial function in patients with coronary risk factors J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1083 - 1088. [Abstract] [Full Text] [PDF]
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S. Setoguchi, M. Mohri, H. Shimokawa, and A. Takeshita Tetrahydrobiopterin improves endothelial dysfunction in coronary microcirculation in patients without epicardial coronary artery disease J. Am. Coll. Cardiol., August 1, 2001; 38(2): 493 - 498. [Abstract] [Full Text] [PDF]
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