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Hypothesis: Sun-produced nitric oxide reduces cardiovascular problems

Dr. Richard Weller, Dermatologist

Found that nitric oxide is produced in the skin by UVA (UVB was not needed))

His 15 minute TedTalk video

More blood flow

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NO Release

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Sunlight Has Cardiovascular Benefits Independently of Vitamin D - 2016 Weller

Blood Purif. 2016;41(1-3):130-4. doi: 10.1159/000441266. Epub 2016 Jan 15.

BACKGROUND:
High blood pressure (BP) is the leading risk factor for disability adjusted life years lost globally. Epidemiological data show a correlation between increased sun exposure and reduced population BP and cardiovascular mortality. Individuals with high serum vitamin D levels are at reduced risk of hypertension, cardiovascular disease and metabolic syndrome, yet multiple trial data show that oral vitamin D supplementation has no effect on these endpoints. Sunlight is a risk factor for skin cancers, but no link has been shown with increased all-cause mortality. Cohort studies from Scandinavia show a dose-dependent fall in mortality with increased sun-seeking behaviour. Skin contains significant stores of nitrogen oxides, which can be converted to NO by UV radiation and exported to the systemic circulation. Human studies show that this pathway can cause arterial vasodilatation and reduced BP. Murine studies suggest the same mechanism may reduce metabolic syndrome.

SUMMARY: Sunlight has beneficial effects on cardiovascular risk factors independently of vitamin D.

KEY MESSAGES:
All-cause mortality should be the primary determinant of public health messages.
Sunlight is a risk factor for skin cancer, but sun avoidance may carry more of a cost than benefit for overall good health.

PMID: 26766556 DOI: 10.1159/000441266
 Download the PDF from VitaminDWiki


Is sunlight good for our heart? Weller 2010

Feelisch M, Kolb-Bachofen V, Liu D, Lundberg JO, Revelo LP, Suschek CV, Weller RB.
Clinical Sciences Research Institute, University of Warwick Medical School, Coventry CV4 7AL, UK. mf at warwick.ac.uk
PMID: 20215123,

Figure in the paper and used in the video

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PDF is attached at the bottom of this page


UVA can produce Nitric Oxide in the blood stream - Weller 2009

{Thanks, Dr. Grant, for finding this study}

Whole body UVA irradiation lowers systemic blood pressure by release of nitric oxide from intracutaneous photolabile nitric oxide derivates.
Circ Res. 2009 Nov 6;105(10):1031-40. doi: 10.1161/CIRCRESAHA.109.207019. Epub 2009 Sep 24.
Opländer C, Volkmar CM, Paunel-Görgülü A, van Faassen EE, Heiss C, Kelm M, Halmer D, Mürtz M, Pallua N, Suschek CV.
Department of Plastic and Reconstructive Surgery, Hand Surgery, and Burn Center, Medical Faculty, RWTH Aachen University, Germany.

RATIONALE: Human skin contains photolabile nitric oxide derivates like nitrite and S-nitroso thiols, which after UVA irradiation, decompose and lead to the formation of vasoactive NO.

OBJECTIVE: Here, we investigated whether whole body UVA irradiation influences the blood pressure of healthy volunteers because of cutaneous nonenzymatic NO formation.

METHODS AND RESULTS: As detected by chemoluminescence detection or by electron paramagnetic resonance spectroscopy in vitro with human skin specimens, UVA illumination (25 J/cm(2)) significantly increased the intradermal levels of free NO. In addition, UVA enhanced dermal S-nitrosothiols 2.3-fold, and the subfraction of dermal S-nitrosoalbumin 2.9-fold. In vivo, in healthy volunteers creamed with a skin cream containing isotopically labeled (15)N-nitrite, whole body UVA irradiation (20 J/cm(2)) induced significant levels of (15)N-labeled S-nitrosothiols in the blood plasma of light exposed subjects, as detected by cavity leak out spectroscopy. Furthermore, whole body UVA irradiation caused a rapid, significant decrease, lasting up to 60 minutes, in systolic and diastolic blood pressure of healthy volunteers by 11+/-2% at 30 minutes after UVA exposure. The decrease in blood pressure strongly correlated (R(2)=0.74) with enhanced plasma concentration of nitrosated species, as detected by a chemiluminescence assay, with increased forearm blood flow (+26+/-7%), with increased flow mediated vasodilation of the brachial artery (+68+/-22%), and with decreased forearm vascular resistance (-28+/-7%).

CONCLUSIONS: UVA irradiation of human skin caused a significant drop in blood pressure even at moderate UVA doses.
The effects were attributed to UVA induced release of NO from cutaneous photolabile NO derivates.

PMID: 19797169

PDF is attached at the bottom of this page


Nitric Oxide and vitamin D - Aug 2014

Aging of the Nitric Oxide System: Are We as Old as Our NO?
J Am Heart Assoc. 2014 Aug 18;3(4). pii: e000973. doi: 10.1161/JAHA.114.000973.
Sverdlov AL, Ngo DT, Chan WP, Chirkov YY, Horowitz JD.

BACKGROUND:
Impaired generation and signaling of nitric oxide (NO) contribute substantially to cardiovascular (CV) risk (CVR) associated with hypertension, hyperlipidemia, and diabetes mellitus. In our rapidly aging society, advanced age is, in itself, a consistent and independent CVR factor. Many processes involved in aging are modulated by NO. We therefore postulated that aging might be independently associated with impaired NO signaling.

METHODS AND RESULTS:
In a prospective cohort study of 204 subjects (mean age 63±6 at study entry), we evaluated the effects of 4 years of aging on parameters of NO generation and effect, including platelet aggregability and responsiveness to NO, and plasma concentrations of the NO synthase inhibitor, asymmetric dimethylarginine (ADMA). Clinical history, lipid profile, high-sensitivity C-reactive protein, routine biochemistry, and 25-hydroxyvitamin D levels were obtained at study entry and after 4 years of follow-up. Aging was associated with marked deterioration of responsiveness of platelets to NO (P<0.0001) and increases in plasma ADMA concentrations (P<0.0001). There was a significant correlation between changes in these parameters over time (r=0.2; P=0.013). On multivariable analyses, the independent correlates of deterioration of responsiveness of platelets to NO were female gender (β=0.17; P=0.034) and low vitamin D concentrations (β=0.16; P=0.04), whereas increases in ADMA were associated with presence of diabetes (β=0.16; P=0.03) and impaired renal function (β=0.2; P=0.004).

CONCLUSIONS:
Aging is associated with marked impairment of determinants of NO generation and effect, to an extent which is commensurate with adverse impact on CV outcomes. This deterioration represents a potential target for therapeutic interventions.

PMID: 25134680
PDF is attached at the bottom of this page


UVA Irradiation of Human Skin Vasodilates Arterial Vasculature and Lowers Blood Pressure Independently of Nitric Oxide Synthase -Weller 2014

Journal of Investigative Dermatology (2014) 134, 1839–1846; doi:10.1038/jid.2014.27; online 20 February 2014
Donald Liu1, Bernadette O Fernandez2, Alistair Hamilton3, Ninian N Lang4, Julie M C Gallagher5, David E Newby4, Martin Feelisch2 and Richard B Weller1,3
1Department of Dermatology, University of Edinburgh, Edinburgh, UK
2Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK
3MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
4BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
5Leithmount Surgery, Edinburgh, UK
Correspondence: Richard B. Weller, or Martin Feelisch, Department of Dermatology, Lauriston Building, Lauriston Place, Edinburgh, EH3 9HA, UK. E-mail: r.weller at ed.ac.uk or Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, Mailpoint 801, South Academic Block Tremona Road, Southampton, SO16 6YD, UK. E-mail: m.feelisch at soton.ac.uk

The incidence of hypertension and cardiovascular disease (CVD) correlates with latitude and rises in winter. The molecular basis for this remains obscure. As nitric oxide (NO) metabolites are abundant in human skin, we hypothesized that exposure to UVA may mobilize NO bioactivity into the circulation to exert beneficial cardiovascular effects independently of vitamin D. In 24 healthy volunteers, irradiation of the skin with two standard erythemal doses of UVA lowered blood pressure (BP), with concomitant decreases in circulating nitrate and rises in nitrite concentrations. Unexpectedly, acute dietary intervention aimed at modulating systemic nitrate availability had no effect on UV-induced hemodynamic changes, indicating that cardiovascular effects were not mediated via direct utilization of circulating nitrate. UVA irradiation of the forearm caused increased blood flow independently of NO synthase (NOS) activity, suggesting involvement of pre-formed cutaneous NO stores. Confocal fluorescence microscopy studies of human skin pre-labeled with the NO-imaging probe diaminofluorescein 2 diacetate revealed that UVA-induced NO release occurs in a NOS-independent, dose-dependent manner, with the majority of the light-sensitive NO pool in the upper epidermis. Collectively, our data provide mechanistic insights into an important function of the skin in modulating systemic NO bioavailability, which may account for the latitudinal and seasonal variations of BP and CVD.


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Attached files

ID Name Comment Uploaded Size Downloads
9873 Sunlight Has Cardiovascular Benefits Independently of Vitamin D.pdf admin 17 May, 2018 10:41 78.96 Kb 8
4302 Aging of the Nitric Oxide System.pdf PDF 2014 admin 20 Aug, 2014 14:47 1.03 Mb 922
2019 UVA Nitrous Oxide - 2009.pdf PDF admin 27 Jan, 2013 14:37 1,001.02 Kb 1208
1971 NO release.jpg admin 18 Jan, 2013 14:32 26.19 Kb 4385
1970 More blood flow.jpg admin 18 Jan, 2013 14:32 29.80 Kb 4730
1968 Nitric F3.jpg admin 18 Jan, 2013 14:11 37.35 Kb 5585
1967 sunlight good for your heart nitric oxide - 2010.pdf PDF admin 18 Jan, 2013 14:11 193.27 Kb 1128
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