How does sulfur smell?

high blood pressure : Gas that smells like rotten eggs controls blood flow

When the smell of lazy ones wafts by, you're probably more disgusted than relaxed. However, scientists have now shown that the gas that smells like rotten eggs, hydrogen sulfide, is produced in certain cells in animals and acts as a muscle relaxant, thereby regulating blood pressure.

Not only does hydrogen sulfide stink, it's also quite toxic. Inhaling air which contains high concentrations of the gas (around 500 ppm) is fatal to humans. But over the past 20 years, a number of studies have shown that the gas can put mice into a kind of artificial coma, which helps minimize the damage caused by a heart attack.

Now Sol Snyder of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues have identified an enzyme that produces hydrogen sulfide in tissues, which helps control blood flow in mice.

To investigate the function of the enzyme called cystathionine gamma-lyase (CSE), Snyder's team genetically engineered mice so that they lack the gene coding for CSE. The results were clear: "If you turn off CSE, you stop the production of hydrogen sulfide in every part of the body except the brain," explains Snyder. And the first thing they found in those mice that didn't produce hydrogen sulfide? High blood pressure - hypertension.

"That's huge," says Matt Whiteman of Peninsula Medical School, University of Exeter, UK, who studies hydrogen sulfide levels in patients with diabetes-associated high blood pressure. He says this is the first research to show that removing CSE increases blood pressure. "This is fantastic news for people like me who work in this field." The research was published in Science (1).

Good gas

Hydrogen sulfide joins nitric oxide as one of the few gaseous signaling molecules. "Now we have another physiological gas," says Whiteman.

Nitric oxide is produced in the endothelium - the squamous epithelial layer which, among other things, lines the blood vessels - and acts as an endothelium-derives relaxing factor (EDRF). Snyder's work identifies hydrogen sulfide as another EDRF, he says. For example, CSE is regulated by a combination of calcium and calmodulin, a calcium-binding protein. This method is similar to the way in which the enzymes that make nitric oxide are regulated.

Snyder's team ruled out other causes of the high blood pressure in the mice, such as kidney damage or other lack of enzymes. They also examined muscle tissue from the blood vessels of the mice that lacked the gene for CSE and found that it was "significantly impaired" compared to the tissue of normal mice.

Snyder and his colleagues are now working on a comparative study to quantify the relative importance of hydrogen sulfide and nitric oxide. However, the magnitude of the effects of hydrogen sulfide on the mice leads Snyder to suggest that the gas could be as important as an EDRF as nitric oxide.

If so, it could open new avenues in the treatment of certain conditions like angina - which uses nitric oxide-based drugs to widen blood vessels and encourage blood flow. Some patients develop intolerance to these drugs, and an alternative may now be on the horizon, says Whiteman.

One of Snyder's team, Rui Wand of Lakehead University in Ontario, Canada, hopes for additional therapeutic benefits. For those looking for a genetic predisposition to high blood pressure, "screening people with hypertension for abnormalities in the CSE enzyme might be a good idea," agrees Snyder.

"And hypertension is just the beginning," says Wang, adding other diseases such as arteriosclerosis, heart failure and heart problems associated with diabetes mellitus.

(1) Yang, G. et al., Science 322, 587-590 (2008)

This article was first published on October 23, 2008 at [email protected] doi: 10.1038 / news.2008.1187. Translation: Sonja Hinte. © 2007, Macmillan Publishers Ltd

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