NK(1) RECEPTORS MEDIATE NEUROGENIC INFLAMMATORY INCREASE IN BLOOD-FLOW IN RAT AIRWAYS

We studied the effect of neurogenic inflammation on airway blood flow in anesthetized F-344 rats. Three successive determinations of blood f low were made by injecting radionuclide-labeled microspheres suspended in 70% dextrose into the left ventricle. A selective agonist of the t achykinin receptor neurokinin1 (NK1) increased airway blood flow, but NK2- and NK3-selective agonists were without effect. The natural agoni st of NK1 receptors, substance P (1 mug/kg), increased airway blood fl ow, an effect that was abolished by the selective NK1 receptor antagon ist CP-99,994 S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine] but n ot by the (2R,3R)-enantiomer CP-100,263. Capsaicin (25 mug/kg), a drug that releases tachykinins and calcitonin gene-related peptide from se nsory nerves, increased airway blood flow, and again this effect was a bolished by CP-99,994. We also studied the effect of a selective inhib itor (captopril, 2.5 mg/kg) of the tachykinin-degrading enzyme kininas e II [or angiotensin-converting enzyme (ACE)] on substance P-induced a irway vasodilation. Captopril potentiated and prolonged the vasodilato r effect of substance P. We conclude that neurogenic vasodilation in r at airways is due to the release of substance P, acts via NK1 receptor s, and may be modulated by ACE.