Interference of glycosylated human hemoglobin with endothelium-dependent responses

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.

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.

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.