There is a growing body of evidence supporting the idea that
nerve growth factor (
NGF) may be involved in the development of
asthma-associated symptoms, such as
airway hyper-responsiveness. Increased levels of
NGF have recently been described in serum and in the airways of asthmatics. We have examined whether exhaled
nitric oxide (NO) levels might be altered during the increased airway responses upon
NGF treatment in guinea-pigs in vivo. Intravenous (i.v.) administration of
histamine normally elicits a rapid peak in insufflation pressure (IP) and in exhaled NO, followed by a period of decreased concentrations of exhaled NO. Anaesthetized guinea-pigs were pre-treated intravenously with either saline, 4 or 80 ng x kg(-1)
NGF 30 min before i.v. challenge with 16 microg x kg(-1)
histamine. At 80 ng x kg(-1)
NGF significantly enhanced the
airway obstruction caused by
histamine, whereas the peak acute increase in exhaled NO was not enhanced. Following the increase, came a rapid drop, an effect enforced in the
NGF treated animals. Subsequently, the time to return to 90% of resting exhaled NO was increased, from 12 min in saline-treated animals to 48 min in
NGF-treated animals. Our data confirm that
NGF can enhance airway responses to
histamine. Moreover, our study shows a decrease in exhaled NO following a
histamine challenge, an effect enhanced by
NGF. A reduced ability to release exhaled NO may be a mechanism for increased airway responses during elevated
NGF levels. The interaction between
NGF and airway NO formation, and its relation to airway responses, merit further investigation.