Reduced inflammation in genetically hypertensive rat airways is associated with reduced tachykinin NK1 receptor numbers

The airways of the genetically hypertensive rat (GH) are hyperinnervated by substance P-containing sensory nerves and exhibit reduced inflammatory responsiveness to substance P and to capsaicin. The present study measured tracheal inflammation to resiniferatoxin (1.0 mu g/kg i.v.), a capsaicin analogue, which lacks the hypotensive action of capsaicin itself, alone or after the neuronal nitric oxide synthase inhibitor 1-(2-trifluoromethylphenyl)imidazole (TRIM) (50 mg/kg i.p.). The inflammatory response to resiniferatoxin alone was 50% lower in untreated GH than in control rats, a similar strain difference to that seen previously with capsaicin. Pre-treatment with TRIM had no effect on inflammation in either strain. Binding kinetics of the tachykinin NK1 receptor antagonist [H-3](S)-1-{2-[3(3,4-dichlorophenyl)-1-(3 -isopropoxyphenylacetyl)piperidin-3-yl]ethyl}-4-phenyl-1-azoniabicyclo[2,2,2,]octane chloride ([H-3]SR140333)-(0.125-16.0 nM) showed 50% reduction of B-max in GH versus control tracheae (74 +/- 13 cf. 165 +/- 26 fmol/mg protein). Our results indicate that the reduced neurogenic inflammatory responsiveness in GH rats can be attributed entirely to reduced tachykinin NK1 receptor numbers. (C) 2000 Elsevier Science B.V. All rights reserved.