Alteration in airway microvascular leakage induced by sensorineural stimulation in rats exposed to inhaled formaldehyde

Inhaled formaldehyde can rapidly produce microvascular leakage in the airway through stimulation of tachykinin NK1 receptors by tachykinins released from sensory nerves. Tachykinin NK1 receptors are known to be internalized in the cytoplasm after being stimulated, thus leading to transient attenuation of their action. We investigated time changes in airway microvascular leakage during formaldehyde inhalation for 45 min, and whether pre-inhalation of formaldehyde (5 ppm, 30 min) decreases the responses induced by subsequent inhaled formaldehyde (5 ppm, 15 min), intravenous capsaicin (75 μg/kg) and intravenous substance P (10 μg/kg) in rat airway. Evans blue dye content extravasated into the tissues was measured as an index of plasma leakage. Formaldehyde rapidly produced dye leakage in the airway, a response that ended within 15 min after the start of formaldehyde inhalation. Pre-inhalation of formaldehyde markedly decreased the responses induced by formaldehyde and capsaicin, but not substance P. However, dye leakage induced by formaldehyde was significantly enhanced by formaldehyde inhalation 20 h earlier. Our results suggest that tachyphylaxis in neurogenic airway microvascular leakage seen after formaldehyde inhalation may be due to impairment of tachykinin release from sensory nerves or decreases in tachykinins within sensory nerves. However, desensitization of tachykinin NK1 receptors was unlikely to be important in the tachyphylactic response.