title: Topical methyl nicotinate-induced skin vasodilation in diabetic neuropathy.
abstract: OBJECTIVE
  To evaluate the vasodilation induced by topical application of methyl nicotinate (MN) and to compare it with the vasodilatory response to acetylcholine (ACh) and sodium nitroprusside (SNP) in healthy subjects and diabetic neuropathic patients.
  
  
  METHODS
  Ten diabetic patients with peripheral neuropathy (DN) and 10 age- and sex-matched healthy control subjects (C) were enrolled. The vasodilatory response to topical application of 1% MN and a placebo emulsion at the forearm and dorsum of the foot skin at 5, 15, 30, 60 and 120 min was measured using Laser Doppler Perfusion Imaging. The vasodilatory response to iontophoresis of 1% ACh and 1% SNP solutions was also evaluated.
  
  
  RESULTS
  The maximal vasodilatory response to ACh, SNP and MN was similar at the forearm and foot level in the diabetic patients. In the control group, the responses to MN, ACh and SNP were similar on the forearm but in the foot, the MN vasodilatory response was higher when compared to the ACh and SNP responses. MN-related vasodilation was present 5 min after the application, reached its peak at 15-30 min and declined to pre-application levels 120 min afterward.
  
  
  CONCLUSIONS
  Topical application of MN at the forearm and foot levels of diabetic neuropathic patients results in skin vasodilation that is comparable to the maximal vasodilation that can be induced by iontophoresis of ACh or SNP and lasts for less than 2 h. Further studies will be required to explore the potential of MN to increase blood flow and to prevent diabetic foot problems in clinical practice.
authors.affiliation: Joslin-Beth Israel Deaconess Foot Center, Department of Surgery, Microcirculation Laboratory, Beth Israel-Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. aveves@caregroup.harvard.edu
authors.forename: Antonella
authors.initials: A
authors.lastname: Caselli
authors.forename: Tarik
authors.initials: T
authors.lastname: Hanane
authors.forename: Brady
authors.initials: B
authors.lastname: Jane
authors.forename: Stephen
authors.initials: S
authors.lastname: Carter
authors.forename: Lalita
authors.initials: L
authors.lastname: Khaodhiar
authors.forename: Aristidis
authors.initials: A
authors.lastname: Veves
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000287:Administration, Topical; D000328:Adult; D016022:Case-Control Studies; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D005528:Foot; D005542:Forearm; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D009539:Nicotinic Acids / Q000008:administration & dosage*; D009599:Nitroprusside / Q000008:administration & dosage; D012867:Skin / Q000098:blood supply*; D013997:Time Factors; D014664:Vasodilation; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D009539:Nicotinic Acids; D014665:Vasodilator Agents; D009599:Nitroprusside; C008473:methyl nicotinate; D000109:Acetylcholine