Naturally Occurring Bronchodilator Protects Laboratory Animals Against Asthma

Jonathan S. Stamler, MD, Ph.D., Howard Hughes Medical Institute and Duke University Medical Center and David Schwartz, MD, MPH, Director, NIEHS
U19ES012496

Background: The incidence of asthma has been steadily growing over the past 30 years. Approximately 15 million people, which include five million children, in the United States alone have asthma. A variety of theories have been postulated for this rise including increased exposure to indoor allergens, air pollutants, and other inflammatory agents. Scientists and doctors have known about the effects of airway constriction on asthma exacerbation for some time. Much research and treatment has focused on airway hyperresponsiveness and chronic inflammation but very little effort has been given to naturally occurring airway relaxants and the balance between constricting and relaxing agents.

Advance: A team of researchers at Duke University, supported by NIEHS and the Howard Hughes Medical Institute, has discovered a naturally occurring bronchodilator that relaxes the airway and helps keep it open. Asthmatic animals and humans are deficient in the compound, which is known as S-nitrosoglutathione (GSNO). In laboratory animal studies, mice exposed to allergens exhibited airway hyperresponsiveness and increased levels of a reductase enzyme that breaks down GSNO and other S-nitrosothiols (SNOs). However, transgenic mice missing the gene for GSNO reductase given the same treatments, showed increases in lung SNOs and didn't develop airway hyperresponsiveness.

Implications: This study shows that GSNO reductase is very important in the regulation of the size of the airway under normal conditions and in response to allergen challenge. Furthermore, a deficiency of SNOs may make fundamental contributions to the development of asthma. Team leader Dr. Jonathan Stamler reports that the findings "suggest that the SNO deficit seen in patients with asthma may result from increased GSNO reductase activity" and that "the enzyme may therefore offer a novel target for therapies designed to alleviate airway obstruction." In addition, GSNO repletion in patients may treat asthmatic symptoms.

Citation: Que LG, Liu L, Yan Y, Whitehead GS, Gavett SH, Schwartz DA, Stamler JS. Protection from experimental asthma by an endogenous bronchodilator. Science. 2005 Jun 10;308(5728):1618-21. Epub 2005 May 26.