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April 28, 2024

Hydrogen sulfide gas has signaling role - Small molecule regulates blood pressure, joins growing class of gases with biological function

By Ann Wang | November 12, 2008

Hydrogen sulfide has a pretty bad reputation. The gas is the culprit for the odor of rotten eggs and the smell of the guy sitting next to you who had Chipotle for dinner. This toxic, flammable product of anaerobic sulfate breakdown can shut down cellular respiration, the cell's energy production mechanism, at high enough concentrations.

However, scientists at the Hopkins School of Medicine, the University of Saskatchewan and Lakehead University have worked together to uncover a natural biological role for the compound, one that is at work in your body right now.

According to the report published in Science, the endothelial cells lining blood vessels in mice actually produce H2S, and the gas is necessary to maintain normal blood pressure. The scientists also discovered the enzyme that produces H2S in the mice.

The team of researchers, including Solomon Snyder of Hopkins, already suspected from previous research that an enzyme called cystathionine gamma-lyase (CSE) manufactures H2S in the body.

Rui Wang of Lakehead University and Lingyun Wu of the University of Saskatchewan, both in Canada, engineered mice with the CSE gene knocked out and tested them against wild type mice with the CSE gene intact. A mouse without CSE should be unable to make any hydrogen sulfide gas.

They found that as the mice aged, those deficient in CSE had virtually no H2S in their bloodstream and had significantly higher blood pressure than wild -type mice. The 20 percent increase in blood pressure observed in these mice is analogous to serious hypertension in an adult human subject.

When the scientists injected the mutant mice with methacholine, a drug that is known to relax blood vessels, there was little change in the blood pressure. When they injected the mutants with H2S, however, their blood pressure fell. This suggests that H2S plays a unique role in regulating the circulatory system.

"[Previously] there was no direct evidence that endogenous CSE deficient can cause any change in the whole body function . . . and no evidence on how CSE is triggered to produce H2S in endothelium," Wang said.

This paper presents several interesting new ideas: first, that CSE is the enzyme responsible for making H2S in the body, and second, that H2S contributes to relaxing blood vessels.

"There was no [previous] evidence that H2S is normally produced by our bodies - other than intestinal bacteria that generate the H2S," Snyder said. "H2S is now established as a major regulator of blood vessels and blood pressure."

Hydrogen sulfide joins a small but growing group of gaseous regulatory molecules known as gasotransmitters. Nitric oxide and carbon monoxide are also members of this group.

All three gases have important functions. Nitric oxide has previously been shown to relax blood vessels, but it is suspected that it plays a different role from H2S. Carbon monoxide is a neurotransmitter and also relaxes blood vessels.

Snyder was the first scientist to demonstrate that nitric oxide gas can also act as a neurotransmitter between cells in the brain. This pioneering work has directly inspired the search for other small gas molecules that can influence or regulate biological systems.

The scientists hope to expand their discoveries to find new treatments for hypertension, arteriosclerosis and other cardiovascular illnesses. They also discovered that CSE is not the enzyme that makes H2S in the brain and are working on finding that enzyme.

Meanwhile, if studying for midterms is stressing you out, maybe you have another justification for a Chipotle break. Go lower your blood pressure.


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