Relationship of airway responsiveness to agents causing bronchoconstriction and cough in sensitized guinea-pigs.
The relationship between airway responsiveness to bronchoconstrictor- and cough-inducing stimuli has been examined in Ascaris suum-sensitized conscious guinea-pigs. Guinea-pigs were sensitized to Ascaris suum [4000 PNU and 100 mg Al(OH)3 i.p. on days 1 and 7] and then challenged with aerosolized antigen on days 21, 28 and 35. At day 35, antigen-exposure produced an early bronchoconstrictor response (EBR) and in about 50% of the animals also a late bronchoconstrictor response (LBR) commencing 4-8 h later. The bronchial responsiveness to inhaled histamine was increased in sensitized guinea-pigs and increased further 20-24 h after acute antigen challenge. Guinea-pigs developing only EBR were equally sensitive to histamine as those having both EBR and LBR. In contrast, the cough and reflex bronchoconstriction produced by inhaled citric acid (0.40 M, acting on capsaicin-sensitive sensory neurons) and cigarette smoke (3 min exposure; exciting both capsaicin-sensitive neurons and rapidly adapting stretch receptors) were not altered by sensitization. Furthermore, acute antigen challenge did not alter the effect of citric acid as measured 24 h later. The antigen-induced airway hyperresponsiveness to histamine was not accompanied by an altered sensitivity of airway sensory nerves mediating cough (and reflex bronchoconstriction), demonstrating that bronchial- (airway obstruction) and sensory- (cough) hyperresponsiveness involve separate and independent mechanisms.
Karlsson
J A
JA
Department of Exploratory Pharmacology, AB Draco, Lund, Sweden.
Zackrisson
C
C
Erjefält
J
J
Forsberg
K
K
D000280:Administration, Inhalation; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage; D017165:Ascaris suum / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000382:microbiology / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D003371:Cough / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D012906:Smoke / Q000009:adverse effects
D000947:Antigens, Helminth; D016085:Bronchoconstrictor Agents; D002951:Citrates; D012906:Smoke; D019343:Citric Acid; D006632:Histamine; D002211:Capsaicin