Red/near infrared light stimulates release of an endothelium dependent vasodilator and rescues vascular dysfunction in a diabetes model

Free Radic Biol Med. 2017 Dec;113:157-164. doi: 10.1016/j.freeradbiomed.2017.09.012. Epub 2017 Sep 19.

Abstract

Peripheral artery disease (PAD) is a morbid condition whereby ischemic peripheral muscle causes pain and tissue breakdown. Interestingly, PAD risk factors, e.g. diabetes mellitus, cause endothelial dysfunction secondary to decreased nitric oxide (NO) levels, which could explain treatment failures. Previously, we demonstrated 670nm light (R/NIR) increased NO from nitrosyl-heme stores, therefore we hypothesized R/NIR can stimulate vasodilation in healthy and diabetic blood vessels. Vasodilation was tested by ex vivo pressure myography in wild type C57Bl/6, endothelial nitric oxide synthase (eNOS) knockout, and db/db mice (10mW/cm2 for 5min with 10min dark period). NOS inhibition with N-Nitroarginine methyl ester (L-NAME) or the NO scavenger Carboxy-PTIO (c-PTIO) tested the specificity of NO production. 4,5-Diaminofluorescein diacetate (DAF-2) measured NO in human dermal microvascular endothelial cells (HMVEC-d). R/NIR significantly increased vasodilation in wild type and NOS inhibited groups, however R/NIR dilation was totally abolished with c-PTIO and blood vessel denudation. Interestingly, the bath solution from intact R/NIR stimulated vessels could dilate light naïve vessels in a NO dependent manner. Characterization of the bath identified a NO generating substance suggestive of S-nitrosothiols or non heme iron nitrosyl complexes. Consistent with the finding of an endothelial source of NO, intracellular NO increased with R/NIR in HMVEC-d treated with and without L-NAME (1mM), yet c-PTIO (100µm) reduced NO production. R/NIR significantly dilated db/db blood vessels. In conclusion, R/NIR stimulates vasodilation by release of NO bound substances from the endothelium. In a diabetes model of endothelial dysfunction, R/NIR restores vasodilation, which lends the potential for new treatments for diabetic vascular disease.

Keywords: Diabetes mellitus; Electromagnetic energy; Endothelial dysfunction; Microcirculation; Nitric oxide; Photobiomodulation.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / enzymology
  • Diabetes Mellitus, Experimental / metabolism*
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / radiation effects
  • Endothelium-Dependent Relaxing Factors / metabolism*
  • Humans
  • Infrared Rays
  • Light*
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism

Substances

  • Endothelium-Dependent Relaxing Factors
  • Nitric Oxide
  • Nitric Oxide Synthase Type III