Hydrogen sulfide discovered to be a major player in the regulation of blood pressure

This news item reveals how intricate and complicated are the biochemical mechanisms which control and keep in harmony various processes in our body.

K.S.Parthasarathy


The heart.org

http://www.theheart.org/viewArticle.do?primaryKey=913773&nl_id=tho23oct08

HEARTWIRE

Hydrogen sulfide discovered to be a major player in the regulation of blood pressure
October 23, 2008 | Michael O'Riordan
Baltimore, MD - Twenty years after US scientists won the Nobel Prize for discovering that nitric oxide (NO) is an important signaling molecule in the cardiovascular system, findings that helped identify the determinants of blood pressure, new research has uncovered yet another gas, hydrogen sulfide (H2S), that acts as a major physiologic vasodilator and regulator of blood pressure.
"Nitric oxide is unique in that it's a gas, and since mediators in the body come in chemical classes, others have wondered whether other gases could do the same sort of thing," said Dr Solomon Snyder (Johns Hopkins University School of Medicine, Baltimore, MD), one of the investigators from the study published in the October 24, 2008 issue of Science.
Made by bacteria in the intestine, H2S has been known for some time to lower blood pressures in animals injected with the gas. Investigators, however, wanted to determine the exact role of H2S as a physiologic vasorelaxant and determinant of blood-pressure levels. Speaking with heartwire, Snyder explained that researchers, including senior investigator Dr Rui Wang (Lakehead University, Thunder Bay, ON), speculated H2S might be made by cystathionine -lyase (CSE), leading to the development of a mouse model in which the gene for CSE was knocked out.
Once the gene for CSE was depleted, the researchers discovered that H2S levels in the serum, heart, aorta, and other tissues were markedly reduced.
"We discovered that in most of the body, except for the brain, hydrogen-sulfide production vanished in the knockout mice," said Solomon. "So we said, 'Aha!' We were then able to characterize these mice to see what changed about them, and of course, the first big question was: Does anything happen to the blood pressure? Sure enough, their blood pressure is markedly elevated, at least as much, if not more so, in mice in which we knock out the gene for making nitric oxide."
Compared with normal mice, blood pressure in the mutant mice peaked at 135 mm Hg when the mice were 12 weeks of age, almost 18 mm Hg higher than in the control mice.
Next steps involved testing how the mesenteric arteries of the mutant mice responded to methacholine, a neurotransmitter that is part of the relaxation pathway. When methacholine was added to the vessels of normal mice, the arteries relaxed. When it was added to the vessels of CSE-knockout mice, however, there was no relaxation of the mesenteric arteries.
"We're going to have to do a lot of work, in lots of blood vessels, and in lots of species of animals, to pin down the relative importance of nitric oxide and hydrogen sulfide, but from our work it is very clear that hydrogen sulfide is a pretty major determinant of how your blood vessels function and your blood pressure," said Snyder.
Although the two gases appear to perform similar functions, Snyder said they are unsure if nitric oxide and H2S work together or are mutually exclusive, a question that will require continued research. In terms of potential long-term clinical implications, H2S could be chemically linked with another molecule, put into a pill, and then released to regulate blood pressure, he added.
Snyder told heartwire the discovery was fascinating and that he could hardly believed the results worked out. "It was just a theory, and we kept doing lots of different experiments, with Rui Wang's lab and with my own lab, and every experiment kept coming out positive. In good science, you do all sorts of experiments to disprove your hypothesis, but nothing disproved this one."
Source
1. Yang G, Wu L, Jiang B, et al. H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine -lyase. Science 2008; 322:587-590.


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