Interference of glycosylated human hemoglobin with endothelium-dependent responses.
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.


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.
Rodríguez-Mañas
L
L
Service of Geriatrics, Hospital Universitario de Getafe, Madrid, Spain.
Arribas
S
S
Girón
C
C
Villamor
J
J
Sánchez-Ferrer
C F
CF
Marín
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D006442:Glycated Hemoglobin / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D000109:Acetylcholine; D000316:Adrenergic alpha-Agonists; D006442:Glycated Hemoglobin; D009569:Nitric Oxide; D009638:Norepinephrine