A range of clinical studies have linked low vitamin D levels to cardiovascular risk factors such as high blood pressure and a range of disease states including diabetes, multiple sclerosis and cancer. While much of this evidence points towards an association between lower levels of the sunshine vitamin and an increased risk, there has yet to be any causal link or underlying molecular mechanisms identified to confirm such suggestions.
Now researchers from the Institute of Physiology, Pathophysiology and Biophysics at the Vetmeduni Vienna, may have identified such a mechanism - finding that prolonged vitamin D deficiency in mice can cause blood vessels to stiffen and become less flexible.
"Vitamin D enhances the production of the enzyme eNOS (endothelial nitric oxide synthase) in the inner layer of blood vessels, the endothelium," explained Olena Andrukhova - who led the research. "This is critical for the regulation of blood pressure."
"The enzyme produces a molecule called nitric oxide (NO), an important factor for the relaxation of smooth muscles in the blood vessels. When too little NO is formed, the vessels become less flexible. This ultimately leads to higher blood pressure which can give rise to other circulatory diseases. So indirectly, vitamin D controls blood pressure."
Mouse data
The team worked with genetically modified mice in which the vitamin D receptors in the animals were changed so that no vitamin D signalling was possible.
Since vitamin D also regulates the body's calcium and phosphate balance, the rodents were given a special diet to ensure that they had enough calcium and phosphorus. The lack of vitamin D was therefore the only deficiency that could have affected the physiology of the animals.
Writing in the journal Molecular Endocrinology, Andrukhova and colleagues revealed that after about a year without vitamin D signalling, the mice had increased blood pressure.
At this time the team conducted a series of studies on various tissues from the animals in order to understand what lies behind the increased blood pressure - finding that the lack of vitamin D signalling was responsible for decreased expression of eNOS, increased deposition of collagen and fewer elastic fibres.
They revealed that over time, the blood vessels of the mice had become more rigid and flexible - the consequence of which was increased blood pressure and changes in cardiac structure and function.
"It is not that vitamin D deficiency will lead immediately to an increase in blood pressure amplitude or blood pressure, but over the long term it can lead to cardiovascular damage," explained Professor Reinhold Erben - a co-author of the study.
"We have to remember that in Central Europe, vitamin D synthesis in the skin is physically impossible from November to February at sea level. Levels of UV-B radiation are just too low. The alternatives are vitamin D supplements or a stay in the mountains."
Source: Molecular Endocrinology
Published online ahead of print, doi: 10.1210/me.2013-1252
"Vitamin D Is a Regulator of Endothelial Nitric Oxide Synthase and Arterial Stiffness in Mice"
Authors: Olena Andrukhova, Svetlana Slavic, et al