Early Endothelial Dysfunction Severely Impairs Skin Blood Flow Response to Local Pressure Application in Streptozotocin-Induced Diabetic Mice

Author:

Sigaudo-Roussel Dominique1,Demiot Claire1,Fromy Bérengère1,Koïtka Audrey1,Lefthériotis Georges1,Abraham Pierre1,Saumet Jean Louis1

Affiliation:

1. From the Laboratoire de Physiologie, Faculté de Médecine d’Angers, Angers, France

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.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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