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CLINICAL STUDIES

Inhibitory effects of low-density lipoproteins from men with type II diabetes on endothelium-dependent relaxation

Karen L. McNeill^*, Luigi Fontana, MD^*, David L. Russell-Jones, FRCP, Iris Rajman, PhD^*, James M. Ritter, FRCP^* and Philip J. Chowienczyk, FRCP^*

^* Department of Clinical Pharmacology, Centre for Cardiovascular Biology and Medicine, King’s College, London, United Kingdom
Department of Endocrinology and Diabetes, King’s College, London, United Kingdom

Manuscript received August 9, 1999; revised manuscript received December 7, 1999, accepted February 2, 2000.

Reprint requests and correspondence: Dr. P. J. Chowienczyk, Department of Clinical Pharmacology, St. Thomas’ Hospital, Lambeth Palace Road, London, SE1 7EH, United Kingdom
phil.chowienczyk{at}kcl.ac.uk

OBJECTIVES

The object of the present study is to determine whether native (n) low-density lipoprotein (LDL) isolated from men with type II diabetes and abnormal endothelial function inhibits endothelium-dependent relaxation more than n-LDL isolated from nondiabetic control subjects.

BACKGROUND

Endothelium-dependent vasodilation is impaired in men with type II diabetes and this may result from qualitative rather than quantitative abnormalities of LDL.

METHODS

Forearm blood flow responses to brachial artery infusions of acetylcholine (endothelium-dependent vasodilator) and nitroprusside (endothelium-independent vasodilator) were measured in 10 men with uncomplicated type II diabetes and 10 nondiabetic men of similar age and with similar plasma concentrations of LDL cholesterol. Native LDL was isolated by discontinuous density gradient ultracentrifugation using EDTA to prevent oxidation. Preconstricted rabbit aortic ring bioassay was used to determine inhibitory properties of n-LDL on endothelium-dependent relaxation by measuring relaxation to acetylcholine (and nitroprusside) in the presence and absence of n-LDL.

RESULTS

Forearm blood flow responses to acetylcholine but not nitroprusside were significantly impaired (p < 0.01) in diabetic men compared with control subjects. Native LDL (10 and 100 µg protein/ml) from diabetic men inhibited relaxation to acetylcholine by 13.9 ± 4.8% and 61.9 ± 7.8% (mean inhibition for all doses ± SE), respectively, whereas n-LDL from control subjects inhibited relaxation by 7.3 ± 3.0% and 23.9 ± 5.7% (p < 0.01 for a difference between diabetic and control n-LDL). Relaxation to nitroprusside was not significantly inhibited by n-LDL.

CONCLUSIONS

A qualitative abnormality of LDL may account for endothelial dysfunction in men with type II diabetes.

Abbreviations and Acronyms   ANOVA = analysis of variance   HDL = high-density lipoprotein   LDL = low-density lipoprotein   n-LDL = native LDL   NO = nitric oxide   TBARS = thiobarbituric acid–reactive substances

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