Reduced inflammation in genetically hypertensive rat airways is associated with reduced tachykinin NK(1) 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 microgram/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.
Department of Physiology, Trinity College Dublin, Dublin, Ireland. cbell@tcd.ie
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Campbell
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Beddy
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Foley
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Bakhle
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Bell
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D011812:Quinuclidines / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D014316:Tritium
D004224:Diterpenes; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D014316:Tritium; C085215:SR 140333; D013373:Substance P; C024353:resiniferatoxin