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Hopkins researchers discover how nitric oxide prevents blood vessel inflammation

Johns Hopkins scientists investigating nitric oxide (NO) - the molecular messenger that contributes to body functions as wide-ranging as cell death, new blood vessel growth and erections - have figured out how it can block blood vessel inflammation and prevent clotting, a process that has long stumped biologists.

Reporting in the Oct. 17 issue of the journal Cell, cardiologist Charles J. Lowenstein, M.D., and his team observed that NO has the power to inhibit endothelial cells lining blood vessels from releasing inflammatory substances.

Normally, these cells activate a process called exocytosis (a release of substances) to start inflammation, releasing packets of molecules into the bloodstream that, like tiny hand grenades, explode and discharge compounds that trigger inflammation. NO can move in and target a protein within the endothelial cells, N-ethylmaleimide-Sensitive Factor (NSF), that stops the process from happening by blocking the ability of NSF to push out the molecules.

"Nitric oxide may regulate exocytosis this way in a variety of diseases," says Lowenstein, an associate professor of medicine at Hopkins. "For example, nitric oxide blocks exocytosis from platelets, preventing blood clots; exocytosis from neurons, decreasing neurotoxicity in strokes; and exocystosis from lymphocytes, reducing autoimmune damage."

The Hopkins scientists discovered NO's protective role in both cells and mice. They added NO to human endothelial cells in culture and discovered that it blocked the release of inflammatory compounds. The researchers then found that platelets stuck to blood vessels more often in mice that could not make NO, compared to normal mice.

The findings already have led Lowenstein's team to develop a novel drug to block exocytosis, thereby acting as an anti-clotting agent. It is a peptide that blocks exocytosis by a mechanism similar to that of nitric oxide. In laboratory tests in mice, the drug prevented tiny, d
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Contact: Karen Blum
kblum@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
17-Oct-2003


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