The age-dependent vasodilatation and endothelial calcium influx induced by elastin peptides are modulated by extracellular glucose level.
Elastin peptides have been shown to produce many biological effects on various cell types, including an endothelium- and NO-dependent vasodilatation mediated by extracellular calcium influx and intracellular calcium elevation. Under normal concentration of extracellular glucose, the vasodilatory effect is observed in adult rats and is lost with age. Here, we have studied the consequences of extracellular glucose level changes on these effects triggered by elastin peptides (10(-4)-10(-3) mg ml(-1)), on 6- and 30-month-old rats, using the tension myography and the patch-clamp techniques. Our results show that low (0 mM) or high (33 mM) extracellular glucose concentrations abolish the extracellular calcium influx induced, under normal glucose level (11 mM), by the elastin peptides in cultured human endothelial cells. Also, low or high glucose abolish the vasodilatory action of elastin peptides observed on aorta rings from adult rats under normal glucose concentration. On the contrary, a dilation of aged rat aorta is observed in the presence of elastin peptides and high glucose, whereas such dilation is not observed when the elastin peptides are added in the presence of normal glucose concentration. In aging, a restoration by high glucose of the NO-dependent vasodilatation induced by elastin peptides could enhance the production of damaging peroxynitrite, potentially altering the structure and function of the blood vessels. These results could be of importance in the evaluation and treatment of aged patients with pathophysiological dysregulations of the circulating glucose level, such as in diabetes, age-related glucose intolerance, or low glucose levels caused by inappropriate glucose control treatments.
Faury
Gilles
G
Laboratoire de Développement et Vieillissement de l'Endothélium, Université Joseph Fourier, Commissariat à l'Energie Atomique, Inserm EMI 0219, DRDC, CEA Grenoble, 17, rue des Martyrs, 38054 Grenoble cedex 9, France. Gilles.Faury@ujf-greoble.fr
Robert
Ladislas
L
Verdetti
Jean
J
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004549:Elastin / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009213:Myography; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D014471:Umbilical Veins / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D004549:Elastin; D005947:Glucose; D002118:Calcium