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.
Campbell
V A
VA
Department of Physiology, Trinity College Dublin, Dublin, Ireland. cbell@tcd.ie
Beddy
P
P
Foley
A
A
Bakhle
Y S
YS
Bell
C
C
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