An international team of scientists has discovered that cells inside the blood vessels of mice – as well as in people – naturally produce hydrogen sulfide (H2S) and this gas controls blood pressure.
H2S is produced in the thin, endothelial lining of blood vessels and regulates blood pressure by relaxing blood vessels. As the newest member of a family of so-called "gasotransmitters", this messenger molecule is akin in function, if not form, to chemical signals like nitric oxide, dopamine, and acetylcholine that relay signals between nerve cells, and excite or put the brakes on mind-brain activities.
Dr. Rui Wang, Vice-President (Research) of Lakehead University and principal author of the paper on these findings published in the October 24, 2008 issue of Science, says, "It's difficult to overestimate the biological importance of hydrogen sulfide or its implications in hypertension as well as diabetes and neurodegenerative diseases. In fact, most human diseases probably have something to do with gasotransmitters."
"Now that we know hydrogen sulfide's role in regulating blood pressure, it may be possible to design drug therapies that enhance its formation as an alternative to the current methods of treatment for hypertension," says Johns Hopkins neuroscientist Dr. Solomon H. Snyder, a co-corresponding author of the paper.
Conducting their investigations using mice missing a gene for an enzyme known as CSE, long suspected as responsible for making H2S, the researchers first measured H2S levels in a variety of tissues in the CSE-deficient mice and compared them to normal mice.
The researchers found that the gas was largely depleted in the cardiovascular systems of the altered mice, engineered by Rui Wang and Lingyun Wu of the University of Saskatchewan, whereas normal mice had higher levels – clear evidence that H2S is normally made by mammalian tissues using CSE.
Next, the scientists applied tiny cuffs to the tails of the mice and measured their blood pressure, noting systolic blood pressure spikes of almost 18 mmHg higher in animals lacking CSE compared with normal mice. In humans the healthiest adult systolic pressure is 120 mmHg or less, and high blood pressure is defined as 140 mmHg or more.
Finally, the team tested how blood vessels of CSE-deficient mice responded to the chemical neurotransmitter methacholine, known to relax normal blood vessels. The blood vessels of the altered mice relaxed hardly at all, indicating that H2S was largely responsible for relaxation.
Because gasotransmitters are highly conserved in mammals, the findings of the research are believed to have broad applications to human physiology and disease.
"In terms of relaxing blood vessels, it looks like H2S might be as important as nitric oxide," Snyder says, referring to the first gasotransmitter that was discovered two decades ago to regulate blood pressure.
Just because these two gas molecules perform similar functions doesn't mean they're redundant, says Wang. "Nature has added on layer upon layer of complexity to provide a better and tighter control of body function – in this case, of blood pressure."
Although CSE, the enzyme that activates H2S, was characterized more than half a century ago, the new work is the first to reveal that its trigger works similarly and involves the same molecules as the trigger for nitric oxide, thus putting into place the final piece of the picture puzzle showing how H2S regulates blood pressure by relaxing blood vessels.
The research was supported by grants from the U.S. Public Health Service and the Canadian Institutes of Health Research (CIHR) as well as a Research Scientist Award from CIHR.
Authors of the paper are Guangdong Yang, Lingyun Wu, Bo Jiang, Wei Yang, Jiansong Qi, Kun Cao, Qinghe Meng, all of the University of Saskatchewan; Rui Wang and Shengming Zhang of Lakehead University; and Asif K. Mustafa, Weitong Mu, and Soloman H. Snyder, all of Johns Hopkins University.