Reduced inflammation in genetically hypertensive rat airways is associated with reduced tachykinin NK 1 receptor numbers

Abstract

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 μg/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 NK 1 receptor antagonist [ 3H]( S)-1-{2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidin-3-yl]ethyl}-4-phenyl-l-azoniabicyclo[2,2,2,]octane chloride ([ 3H]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 NK 1 receptor numbers.