Impairment of Endothelium-Dependent Relaxation by Increasing Percentages of Glycosylated Human Hemoglobin
- 1 October 1996
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Hypertension
- Vol. 28 (4), 583-592
- https://doi.org/10.1161/01.hyp.28.4.583
Abstract
High levels of glycosylated human hemoglobin impair nitric oxide–mediated responses. However, the percentage of glycosylation for which this effect is observed and the mechanisms involved are unknown. We tested endothelium-dependent relaxations caused by acetylcholine in rat aortic segments either in control conditions or after preincubation with increasing percentages of glycosylated human hemoglobin. Human hemoglobin (1 and 10 nmol/L) inhibited endothelium-dependent relaxations only when glycosylated at 9% or higher. We evaluated the effect of 14% glycosylated human hemoglobin on acetylcholine-evoked responses in vessels preincubated with scavengers of superoxide anions, hydroxyl radical, or hydrogen peroxide (superoxide dismutase, deferoxamine, and catalase, respectively); with inhibitors of xanthine oxidase, cyclooxygenase, or thromboxane synthase (allopurinol, indomethacin, and dazoxiben, respectively); with blockers of thromboxane A 2 /prostaglandin H 2 or endothelin receptors (SQ 30741 and BQ-123); and with the precursor of nitric oxide synthesis l -arginine. Superoxide dismutase abolished the effect of glycosylated hemoglobin, and the other substances did not have any effect. Glycosylated hemoglobin at 14% did not modify either the vasoconstrictions induced by the blocker of nitric oxide synthase N G -nitro- l -arginine methyl ester or the relaxations evoked in deendothelialized vessels by sodium nitroprusside and 8-bromo-cGMP. However, it inhibited the vasodilations evoked by exogenous nitric oxide. Superoxide dismutase abolished this latter effect. We conclude that the threshold for glycosylated human hemoglobin (Hb A 1 ) to inhibit endothelium-dependent relaxation is 9%. This effect is due to interference with endothelial nitric oxide by means of superoxide anion production.Keywords
This publication has 38 references indexed in Scilit:
- Glycosylated Hemoglobin and the Risk of Retinopathy in Insulin-Dependent Diabetes MellitusNew England Journal of Medicine, 1995
- Fat Embolism SyndromeNew England Journal of Medicine, 1994
- National High Blood Pressure Education Program Working Group report on hypertension in diabetes.Hypertension, 1994
- Role of endothelium in endothelin-evoked contractions in the rat aorta.Hypertension, 1993
- Diabetes mellitus and hypertension.Hypertension, 1992
- Intensified conventional insulin treatment retards the microvascular complications of insulin‐dependent diabetes mellitus (IDDM): the Stockholm Diabetes Intervention Study (SDIS) after 5 yearsJournal of Internal Medicine, 1991
- Production of endothelin-1 from the mesenteric arteries of streptozotocin-induced diabetic ratsLife Sciences, 1991
- Free radical generation by early glycation products: A mechanism for accelerated atherogenesis in diabetesBiochemical and Biophysical Research Communications, 1990
- Thromboxane A2 receptor antagonists inhibit endothelium-dependent contractions.Hypertension, 1990
- Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta.JCI Insight, 1990