Mechanisms of the cutaneous vasodilator response to local external pressure application in rats: involvement of CGRP, neurokinins, prostaglandins and NO

Fromy, Bérengère; Merzeau, Sandra; Ábrahám, Pierre; Saumet, J. L.

doi:10.1038/sj.bjp.0703685

Cited by 68 publications

(97 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…e recently reported a mechanism that allows skin blood flow to increase in response to progressive locally applied pressure in humans (1) and rats (2). The pressure applied is a nonpainful stimulation, but we showed that pressure-induced vasodilation (PIV) involved nerve C fibers, because it disappeared after chronic treatment with capsaicin in animals and humans (1,2).…”

mentioning

confidence: 88%

See 1 more Smart Citation

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

Sigaudo‐Roussel¹,

Demiot²,

Fromy³

et al. 2004

Diabetes

Self Cite

View full text Add to dashboard Cite

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. Diabetes

show abstract

mentioning

confidence: 88%

“…The pressure applied is a nonpainful stimulation, but we showed that pressure-induced vasodilation (PIV) involved nerve C fibers, because it disappeared after chronic treatment with capsaicin in animals and humans (1,2). In addition, Fromy et al.…”

mentioning

confidence: 99%

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

Sigaudo‐Roussel¹,

Demiot²,

Fromy³

et al. 2004

Diabetes

Self Cite

View full text Add to dashboard Cite

show abstract

“…This transient pressure-induced vasodilation (PIV) appears to be a protective cutaneous response. This response was observed both on the hand in humans (5,6) and on the skin of the head in rats (7). This mechanism disappears after desensitization of primary afferents by capsaicin in animals and humans (6,7).…”

mentioning

confidence: 96%

“…This response was observed both on the hand in humans (5,6) and on the skin of the head in rats (7). This mechanism disappears after desensitization of primary afferents by capsaicin in animals and humans (6,7). Therefore, we speculated that the PIV, relying on unmyelinated afferent excitation, could be a missing link between neuropathy and foot ulcer in diabetes.…”

mentioning

confidence: 99%

Impaired Pressure-Induced Vasodilation at the Foot in Young Adults With Type 1 Diabetes

et al. 2004

Self Cite

View full text Add to dashboard Cite

Vascular and neurological mechanisms are both likely to be involved in foot ulcer. We recently reported a pressure-induced vasodilation (PIV), relying on unmyelinated afferent excitation. We previously found that cutaneous blood flow in response to locally applied pressure might be impaired in diabetic patients because of the combined effects of low cutaneous temperature and alterations in microcirculatory function. Therefore, we aimed to analyze whether, at a relatively high cutaneous temperature, PIV is present in type 1 diabetes and to assess endothelial-dependent vasodilation and endothelium-independent vasodilation. We measured cutaneous blood flow using laser Doppler flowmetry on the head of the first metatarsus in response to applied pressure at 5.0 mmHg/min in warm conditions (29.5 ؎ 0.2°C). Responses to iontophoresis of acetylcholine (endothelium dependent) and sodium nitroprusside (endothelium independent) were measured using laser Doppler flowmetry in the forearm. The data indicate that PIV exists at the foot level in normal subjects, whereas it was not found in diabetic patients. In diabetic patients, the nonendothelial-mediated response to sodium nitroprusside was preserved, whereas the endothelial-mediated response to acetylcholine was impaired. These findings might be relevant to the high prevalence of foot ulcer that occurs in diabetic patients. Diabetes 53: [721][722][723][724][725] 2004

show abstract

“…The increase in cutaneous blood flow induced by local pressure application delays the occurrence of tissue ischemia, thus protecting the skin against pressure. The mechanism of pressure-induced vasodilation involves pressure sensing by specialized capsaicin sensory neurons that act at the endothelial level to synthesize and release endothelial factors, such as nitric oxide (NO) (3,4), that induce smooth muscle relaxation. Therefore, neurovascular interaction is crucial for pressure-induced vasodilation development.…”

mentioning

confidence: 99%

Aldose Reductase Pathway Inhibition Improved Vascular and C-Fiber Functions, Allowing for Pressure-Induced Vasodilation Restoration During Severe Diabetic Neuropathy

et al. 2006

Self Cite

View full text Add to dashboard Cite

Pressure-induced vasodilation, a neurovascular mechanism relying on the interaction between mechanosensitive Cfibers and vessels, allows skin blood flow to increase in response to locally nonnociceptive applied pressure that in turn may protect against pressure ulcers. We expected that severe neuropathy would dramatically affect pressure-induced vasodilation in diabetic mice, and we aimed to determine whether pressure-induced vasodilation alteration could be reversed in 8-week diabetic mice. Control and diabetic mice received no treatment or sorbinil, an aldose reductase inhibitor, or alagebrium, an advanced glycation end product breaker, the last 2 weeks of diabetes. Laser Doppler flowmetry was used to evaluate pressureinduced vasodilation and endothelium-dependent vasodilation after iontophoretic delivery of acetylcholine (ACh). We assessed the nervous function with measurements of motor nerve conduction velocity (MNCV) as well as the C-fiber-mediated nociception threshold. Pressure-induced vasodilation, endothelial response, C-fiber threshold, and MNCV were all altered in 8-week diabetic mice. None of the treatments had a significant effect on MNCV. Although sorbinil and alagebrium both restored ACh-dependent vasodilation, sorbinil was the sole treatment to restore the C-fiber threshold as well as pressure-induced vasodilation development. Therefore, the inhibition of aldose reductase pathway by sorbinil improved vascular and C-fiber functions that allow pressure-induced vasodilation restoration that could limit neuropathic diabetic cutaneous pressure ulcers.

show abstract

Mechanisms of the cutaneous vasodilator response to local external pressure application in rats: involvement of CGRP, neurokinins, prostaglandins and NO

Cited by 68 publications

References 84 publications

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

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

Impaired Pressure-Induced Vasodilation at the Foot in Young Adults With Type 1 Diabetes

Aldose Reductase Pathway Inhibition Improved Vascular and C-Fiber Functions, Allowing for Pressure-Induced Vasodilation Restoration During Severe Diabetic Neuropathy

Contact Info

Product

Resources

About