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Circulation, Vol 88, 2111-2116, Copyright © 1993 by American Heart Association

ARTICLES

Interference of glycosylated human hemoglobin with endothelium- dependent responses

L Rodriguez-Manas, S Arribas, C Giron, J Villamor, CF Sanchez-Ferrer and J Marin
Service of Geriatrics, Hospital Universitario de Getafe, Madrid, Spain.

BACKGROUND. Hypertension and other vascular diseases are more prevalent in diabetic patients than in the general population. In humans and in several animal models of diabetes, a disturbance of endothelium- dependent responses has been shown. Oxyhemoglobin is one of the most known modulators of these endothelium-dependent responses. We postulate that high levels of plasmatic glycosylated hemoglobin, a frequent profile in diabetic patients, may be the cause of the disturbance in endothelium-dependent relaxation and/or contraction. METHODS AND RESULTS. Endothelium-dependent responses to acetylcholine and several alpha-adrenergic agonists (norepinephrine, methoxamine, and clonidine) were tested in segments of rat aorta. Experiments were carried out in control segments and in those preincubated with several concentrations of nonglycosylated, low-glycosylated (7.3%), and high-glycosylated (14%) human hemoglobin. Low concentrations of high-glycosylated human hemoglobin (1 to 100 nmol/L) but not of low- or nonglycosylated hemoglobin, inhibited endothelium-dependent relaxation caused by acetylcholine in intact vessels. The same effect was observed on relaxations caused by nitric oxide in denuded ones. High-glycosylated human hemoglobin (10 nmol/L) induced an increase in norepinephrine- evoked contraction in intact vessels; this latter effect was also shown in vessels contracted with methoxamine but not with clonidine. De- endothelialization of the vascular segments blunted these effects of high-glycosylated human hemoglobin. CONCLUSIONS. High glycosylation of human hemoglobin impairs endothelium-mediated vasoactive responses and may play a pathophysiological role in producing hypertension and vascular diseases in diabetic patients.

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