title: Early endothelial dysfunction severely impairs skin blood flow response to local pressure application in streptozotocin-induced diabetic mice.
abstract: Pressure-induced vasodilation (PIV) is a mechanism whereby skin blood flow increases in response to progressive locally applied pressure. Skin blood flow in response to applied pressure decreased early in diabetic patients as a result of vascular and/or neural impairment. This study was designed to determine the effect of vascular changes on PIV in 1-week streptozotocin-induced diabetic mice. We assessed cutaneous microvascular response to local increasing pressure application measured by laser Doppler flowmetry (LDF) and endothelium-dependent and -independent vasodilation by iontophoretic delivery of acetylcholine and sodium nitroprusside and sciatic motor nerve conduction velocity and morphometry. In control mice, LDF increased 34% from baseline to 0.2 kPa external pressure, showing PIV response. In contrast, diabetic mice had no LDF increase in response to progressive external pressure. Moreover, after iontophoretic delivery of acetylcholine, endothelium-dependent vasodilation was largely attenuated in diabetic mice (25%) compared with control mice (81%), whereas vasodilation to sodium nitroprusside was not different between groups. Nerve function as assessed by sciatic nerve conduction velocity and morphometry did not differ between groups. These findings suggest that endothelial impairment is sufficient to severely alter PIV response, which seems to be highly sensitive to endothelial nitric oxide levels. PIV suppression could favor diabetes complications such as diabetic foot ulcers.
authors.affiliation: Laboratoire de Physiologie, Faculté de Médecine d'Angers, 49045 Angers cedex, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Sigaudo-Roussel
authors.forename: Claire
authors.initials: C
authors.lastname: Demiot
authors.forename: Bérengère
authors.initials: B
authors.lastname: Fromy
authors.forename: Audrey
authors.initials: A
authors.lastname: Koïtka
authors.forename: Georges
authors.initials: G
authors.lastname: Lefthériotis
authors.forename: Pierre
authors.initials: P
authors.lastname: Abraham
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Saumet
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D019270:Fructosamine / Q000097:blood; D008297:Male; D051379:Mice; D009046:Motor Neurons; D009431:Neural Conduction; D011312:Pressure; D012039:Regional Blood Flow; D012584:Sciatic Nerve / Q000473:pathology; D012867:Skin / Q000098:blood supply*
chemical_list: D001786:Blood Glucose; D019270:Fructosamine