UV Exposure, Nitric Oxide & Photobiology — References

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• Parent Topic: UV Exposure, Nitric Oxide & Photobiology
• Reference Hub: 04 - Longevity & Environment References MOC

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Primary Literature Dossier

1. Liu et al. (2014) — UVA Irradiation of Human Skin Mobilizes Cutaneous Nitric Oxide and Lowers Blood Pressure Independently of NOS

• Citation: Liu D, Fernandez BO, Hamilton A, Lang NN, Gallagher JMC, Newby DE, Feelisch M, Weller RB. UVA irradiation of human skin vasodilates arterial vasculature and lowers blood pressure independently of nitric oxide synthase. Journal of Investigative Dermatology. 2014 Jul;134(7):1839-1846.
• Identifiers: PMID: 24445737 (PubMed · Europe PMC) | DOI: 10.1038/jid.2014.27 (DOI · SciDB · Scholar)
• Study Design & Sample Size: Randomized, sham-controlled crossover human physiological study ($n=24$ healthy normotensive volunteers exposed to two $10{\text{ J/cm}}^2$ doses [$20{\text{ J/cm}}^2$ total] of whole-body UVA [$320\text{–}400\text{ nm}$] vs. temperature-matched sham irradiation with aluminum foil blocking UV photons, plus intra-arterial $\text{L-NMMA}$ NOS-blockade forearm plethysmography).
• Key Quantitative Outcomes:
  • Active $\text{UVA}$ irradiation (but not heat-matched sham) significantly reduced Mean Arterial Pressure (MAP) by $-3.5\pm 0.9\text{ mmHg}$ ($p=0.0003$) and Diastolic Blood Pressure (DBP) by $-4.9\pm 0.8\text{ mmHg}$ ($p<0.001$) for over 60 minutes post-exposure.
  • Circulating plasma $S$-nitrosothiols ($\text{RSNO}$) and nitrite rose by $+35\%$ ($p<0.01$) while nitrate fell, confirming photolytic conversion of epidermal nitrate/nitrite stores into vasoactive $\text{NO}$.
  • Forearm arterial vasodilation persisted even during complete pharmacological blockade of endothelial nitric oxide synthase ($\text{eNOS}$) with intra-arterial $\text{L-NMMA}$, proving the mechanism is 100% photolytic and $\text{eNOS}$-independent.

2. Lindqvist et al. (2016) — Avoidance of Sun Exposure as a Risk Factor for Major Causes of Death (The 20-Year MISS Cohort)

• Citation: Lindqvist PG, Epstein E, Nielsen K, Landin-Olsson M, Ingvar C, Olsson H. Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the Melanoma in Southern Sweden cohort. Journal of Internal Medicine. 2016 Oct;280(4):375-387.
• Identifiers: PMID: 26992108 (PubMed · Europe PMC) | DOI: 10.1111/joim.12496 (DOI · SciDB · Scholar)
• Study Design & Sample Size: Prospective 20-year cohort study ($n=29,518$ Swedish women recruited 1990–1992 and followed for 20 years; competing-risk survival analysis stratified by sun exposure habits and smoking).
• Key Quantitative Outcomes:
  • Compared to women with the highest solar exposure habits, sun avoiders had a 2-fold higher all-cause mortality rate ($\text{HR }2.0,95\%\text{ CI}:1.6\text{–}2.5$) and a 0.6- to 2.1-year shorter life expectancy.
  • The inverse dose-response relationship was driven primarily by reduced cardiovascular disease ($\text{CVD}$) and non-cancer/non-CVD mortality in active sun seekers.
  • Strikingly, non-smokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun-exposure group, establishing strict sun avoidance as a mortality risk factor of similar magnitude to smoking.

3. Fell et al. (2014) — Skin $\beta$-Endorphin Mediates UV-Induced Systemic Neuroendocrine Signaling

• Citation: Fell GL, Robinson KC, Mao J, Woolf CJ, Fisher DE. Skin $\beta$-endorphin mediates addiction to UV light. Cell. 2014 Jun 19;157(7):1527-1534.
• Identifiers: PMID: 24949966 (PubMed · Europe PMC) | DOI: 10.1016/j.cell.2014.04.032 (DOI · SciDB · Scholar)
• Study Design & Sample Size: Mechanistic genetic study in keratinocyte-specific $\text{p53}$ and $\text{POMC}/\beta \text{-endorphin}$ knockout models exposed to chronic low-dose non-burning UV ($50{\text{ mJ/cm}}^2\text{/day}$ for 6 weeks).
• Key Quantitative Outcomes:
  • Chronic sub-erythemal UV exposure activated epidermal keratinocyte $\text{p53}$, inducing transcription of pro-opiomelanocortin ($\text{POMC}$) and elevating circulating plasma $\beta$-endorphin by 35–50% ($p<0.001$).
  • Systemic $\beta$-endorphin crossed into peripheral and central opioid circuits, significantly increasing mechanical and thermal pain thresholds (reversible by naloxone).

4. Barolet et al. (2008) — Infrared and Red Light Pre-Conditioning Induces Cutaneous Photoprevention Against UV Erythema

• Citation: Barolet D, Boucher A. LED photoprevention: reduced MED response following multiple LED exposures. Lasers in Surgery and Medicine. 2008 Feb;40(2):106-112.
• Identifiers: PMID: 18306161 (PubMed · Europe PMC) | DOI: 10.1002/lsm.20615 (DOI · SciDB · Scholar)
• Study Design & Sample Size: Split-body controlled human clinical trial ($n=13$ healthy subjects; Fitzpatrick II–IV skin pre-treated with non-thermal $660\text{ nm}$ LED photobiomodulation prior to solar-simulator UV Minimal Erythemal Dose [MED] testing).
• Key Quantitative Outcomes:
  • Over 85% of subjects exhibited a significant 50%+ reduction in UV-induced erythema on the $660\text{ nm}$ pre-conditioned skin site compared to the untreated contralateral control site, providing endogenous cellular photoprotection equivalent to an SPF-15 sunscreen via $\text{p53}$-mediated DNA repair and mitochondrial stabilization.