Ultraviolet a irradiation on human skin : nitric oxide mediated cardiovascular responses

Abstract

Cardiovascular disease (CVD) such as hypertension and stroke are serious illnesses that impact on the lives of millions all over the world, with 972 million (26% of the world’s population) suffering from hypertension in year 2000, and an estimated 1.56 billion to be affected by 2025. Hypertension, being one of the most common CVD is associated with the development of stroke, peripheral vascular diseases, myocardial infarction, renal failure as well as cardiac failure. Several studies have shown a seasonal correlation for both the systolic and diastolic blood pressure in mankind. A hypertension trial done by the Medical Research Council in the 1980s showed the average blood pressure being lower in summer than winter, and this difference was more significant in the elderly than the younger population. Other than seasonal variation, blood pressure (including hypertension prevalence) is also noted to correlate with latitude, being higher at places further away from the equator. Other cardiovascular related diseases such as stroke and acute coronary syndrome are also shown occur more frequently in winter. The morbidity and mortality of CVD could be due to various factors including diet, culture, race and social status, but within the United Kingdom, all cause mortality (with cerebral-vascular disease being the major one) correlates with latitude even after accounting for all known risk factors, with CVD risks highest in the north. We propose that this difference in cardiovascular mortality is caused by variations in ultraviolet exposure other than temperature. Known mechanisms of sunlight exposure that affect cardiovascular health include temperature and the ultraviolet B (UVB) mediated photolysis of 7-dehydrocholesterol in the skin to produce 1,25 dihydroxycholecalciferol (Vitamin D). UVB is however a potent skin carcinogen, and calculating risk-benefit ratios for exposure will be important. We believe that independently of vitamin D, nitric oxide plays an important role in blood pressure regulation and cardiovascular health, accounting for seasonal and latitude variation. In 1961, Furchgott demonstrated relaxation of rabbit aorta by irradiating them with ultraviolet light, and in later research he noted this effect is most significant in the ultraviolet A (UVA) spectrum. Recently, Mowbray showed a rich store of various nitro-species within human skin and Oplander showed a reduction of blood pressure in human after giving whole body UVA irradiation. We therefore hypothesize that independently of vitamin D, NO mediates the UVA induced beneficial effects on cardiovascular health. To support our hypothesis, in vivo as well as in vitro studies were conducted. We recruited a total of 63 healthy volunteers and monitored blood pressure, forearm blood flow as well as other cardiovascular parameters before and after UVA irradiation. Blood samples were also taken for the measurement of circulatory nitro-species. We have noted a significant reduction of blood pressure (from 84.5±1.76 to 81.33±1.37 mmHg) and increased forearm blood flow (1.95±0.28 to 2.94±0.47 mL/100mL of tissue/min) after UVA irradiation of human skin; simultaneously, we also noted a rise in circulatory nitrite (0.5±0.04 μM before irradiation to 0.72±0.04 μM) and a drop in circulatory nitrate (11.79±0.64 μM before irradiation and 8.99±0.4 μM). For us to further clarify the role of nitric oxide in different latitude, a monochromator machine that generates specific wavelength of light was been used to irradiate aqueous nitrite solution, and the total amount of nitric oxide release at different latitude was then calculated according to the irradiance of various wavelength across the globe. The results of our studies provide evidence suggesting that nitric oxide release induced by UVA irradiation of the skin can account for the difference in cardiovascular mortality and morbidity by latitude. The current public health advice of avoiding sun exposure to reduce the risk of developing skin cancer may need to be modified.