Researchers have uncovered a natural bronchodilator that protects mice from asthma, offering a new target for treating the potentially fatal condition.

Difficult breathing associated with airway hyperresponsivity and chronic inflammation characterizes asthma, which affects 15 million Americans, including ∼5 million children. Asthma research has generally focused on elucidating the mechanisms that cause the airways to constrict, and has devoted little attention to the idea that the problem may actually lie in the inability of the airways to relax following constriction. Now, a research team led by Jonathan S. Stamler, a professor of medicine at Duke University Medical Center (Durham, NC), has shown in mice that failure of affected airways to relax may be more important to the pathology of an asthma attack than previously thought.

Although nitric oxide (NO) is thought to regulate airway tone, researchers have not been able to affect allergen response by manipulating NO levels in mice. Stamler's group looked at the role of an NO-carrying compound, S-nitrosoglutathione (GSNO), on airway constriction and dilation (Science, 10 June).

When challenged with an allergen, the airway lining fluid of wild-type mice prone to asthma showed reduced levels of GSNO, associated with elevated levels of GSNO reductase (GSNOR), the enzyme that breaks down GSNO. Challenge with a control substance (PBS) did not result in detectable levels of GSNOR in the airway lining fluid. On the other hand, GSNOR knockout mice, which do not produce the enzyme, show elevated levels of GSNO and do not develop asthmatic symptoms when exposed to an allergen.

This study also calls into question the traditional notion that inflammation has a role in the pathogenesis of asthma. Stamler's team found comparable inflammatory responses, characterized by the presence of eosinophils, interleukin-13, and IgG antibodies, in wild-type and GSNOR knockout mice exposed to PBS or allergen.

Finding ways to increase GSNO levels, either by administration of the compound or inhibition of GSNOR, may lead to new ways to treat asthma in humans. Stamler tells Lab Animal that the group's future plans include “assessment of GSNO/GSNOR levels in asthmatic patient populations, search for inhibitors of GSNOR, and hopefully test[ing of] GSNO in clinical trials.”