Anyone with a nose knows the rotten-egg odor of hydrogen sulfide, a gas generated by bacteria living in the human colon. Now an international team of scientists has discovered that cells inside the blood vessels of mice — as well as in people, no doubt — naturally make the gassy stuff, and that it controls blood pressure. Having discovered that hydrogen sulfide, or H2S, is produced in the thin, endothelial lining of blood vessels, the researchers, including scientists from Johns Hopkins, now report in Science that H2S 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.

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 hydrogen sulfide might be as important as nitric oxide," Snyder says, referring to the first gasotransmitter that two decades ago was discovered to regulate blood pressure. Just because these two gas molecules perform similar functions, doesn't mean they're redundant, says Wang, the paper's principal author. "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."
Studying gaseous messengers can be tricky, explains Snyder, an authority on nitric oxide (NO) whose lab in 1990 discovered that the enzyme triggering NO production is activated by a protein mechanism known as calcium-calmodulin.
"When a nerve fires, it releases a bit of neurotransmitter. Then it fires again, very quickly, and releases more of the neurotransmitter, which is always in reserve and at the ready in large storage pools called vesicles. However, gasses can't be stored; they diffuse. So every time there's a nerve impulse, an enzyme must be activated to make it," he says."
Although CSE, the enzyme that activates hydrogen sulfide, was characterized more than half a century ago, the new work is the first to reveal that it is activated in the same way as the nitric oxide-forming enzyme, thus establishing how hydrogen sulfide regulates blood pressure by relaxing blood vessels.
"It's difficult to overestimate the biological importance of hydrogen sulfide or its implications in hypertension as well as diabetes and neurodegenerative diseases," Wang says. "In fact, most human diseases probably have something to do with gasotransmitters." The research was supported by grants from the U.S. Public Health Service and the Canadian Institutes of Health Research as well as a Research Scientist Award.
Credits: John Hopkins Inst.
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