More recently, evidence from the Duke group has indicated that a family of NO-carrying molecules called S-nitrosothiols (SNOs) might mediate NO's role throughout the body, and offer new therapeutic approaches to diseases of the heart, lung and blood.

Last year the researchers showed that SNOs played a critical role in septic shock, a common cause of death in intensive care units. Earlier this year they showed that SNOs are deficient in the blood of patients with sickle cell disease. Now, the link between GSNO deficiency and asthma further suggests that SNOs might play a protective role in many diseases.

In the current study, Stamler's team examined the airway responses of normal mice and those lacking an enzyme called GSNO reductase, which breaks down SNOs. The Duke researchers earlier showed that the enzyme governs GSNO levels in many tissues, including the lung.

Normal mice prone to asthma exhibit increased GSNO reductase levels, resulting in lower concentrations of lung GSNO following allergen exposure, the researchers found. In contrast, mice with elevated GSNO were protected from the airway hyper-reactivity that makes breathing difficult in asthma.

"Our findings indicate that GSNO reductase is critical for regulation of airway tone under normal conditions and in response to allergic challenge, and that an imbalance of GSNO, and perhaps of other S-nitrosothiols, may contribute fundamentally to asthma," Stamler said.

"Our results further suggest that the GSNO deficit seen in patients with asthma may result from increased GSNO reductase activity," he continued. "The enzyme may therefore offer a novel target for therapies designed to alleviate airway obstruction."

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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-660-1306
Duke University Medical Center
26-May-2005