Inhibitory actions of prostaglandin E₁ on neurogenic plasma extravasation in rat airways

To determine whether neurogenic inflammation can be inhibited by prostaglandin E₁ (PGE₁), that is suggested to have an inhibitory effect on neuropeptide release from airway sensory nerves, we examined plasma extravasation in the airways of anesthetized rats in vivo with Evans blue due as a marker. Neurogenic inflammation was produced by an i.v. injection of capsaicin (100 μg/kg) or by antidromic electrical stimulation of the right vagus nerve (4 Hz, 1 ms, 4 V for 1 min). Capsaicin injection significantly increased leakage of dye in the trachea and main bronchi. Similar increases in leakage were seen in the trachea and right bronchus on electrical stimulation of the right vagus nerve. PGE₁ (1-1000 μg/kg) inhibited the leakage induced by capsaicin in the trachea and bronchi concentration dependently with complete inhibition at a concentration of 1000 μg/kg. Likewise, PGE₁ (1000 μg/kg) significantly inhibited electrical stimulation-induced leakage in the trachea and right bronchus (P < 0.01). I.v. substance P (SP; 1 μg/kg) increased Evans blue dye extravasation in the same way as the leakage induced by capsaicin and electrical stimulation but PGE₁ (1000 μg/kg) failed to inhibit SP-induced leakage in the trachea and main bronchi (P > 0.20). These results suggest that PGE₁ inhibits neurogenic plasma leakage by presynaptic inhibition of the release of neuropeptides from sensory nerves.