Bronchoconstrictor reactivity to NKA in allergic dogs: a comparison to histamine and methacholine.
Airway hyperresponsiveness to neurokinin A (NKA) occurs in inflammatory airway diseases like asthma. In this study, bronchoconstrictor reactivity to NKA was measured in beagle dogs neonatally sensitized to and challenged with ragweed. Comparisons were made to histamine and methacholine. Lung resistance (R(L)) and dynamic lung compliance (C(Dyn)) were measured in anesthetized, spontaneously breathing dogs before and after aerosol challenge with NKA, histamine or methacholine. The concentration of these agents increasing R(L)by 25% above baseline (PC(25)) was calculated before and 24 h after aerosolized ragweed challenge. Before ragweed, the bronchoconstrictor reactivity to NKA was four-fold higher in ragweed-sensitized dogs (PC(25)=0.036+/-0.006%) compared to non-sensitized controls (PC(25)=0.177+/-0.030%, P<0.05). On the other hand, there was no difference in the bronchoconstrictor reactivity to histamine or methacholine between these two groups. Twenty-four hours after ragweed challenge to sensitized dogs, NKA reactivity was unchanged from pre-ragweed values but histamine and methacholine reactivity was increased by 2-3-fold. These results demonstrate airway hyperresponsiveness to NKA, histamine and methacholine in allergic beagle dogs although hyperresponsiveness to NKA exists in these allergic dogs before an antigen challenge. This animal model may prove to be useful to evaluate the role of tachykinins in hyperractive airway diseases.
Allergy, Schering-Plough Research Institute Kenilworth, New Jersey, 07033, USA
A
A
House
C
C
Celly
S
S
Young
W
W
Kreutner
R W
RW
Chapman
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000503:physiopathology*; D001986:Bronchial Spasm / Q000139:chemically induced; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology*; D004285:Dogs; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006967:Hypersensitivity / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D015288:Neurokinin A / Q000494:pharmacology*
D000336:Aerosols; D016210:Methacholine Chloride; D006632:Histamine; D015288:Neurokinin A