The influence of atropine and cromolyn on human bronchial hyperreactivity to aerosolized prostaglandin F2 alpha.
The mechanism of prostaglandin F2 alpha(PGF2alpha)-induced airway constriction was explored by determining the influence of atropine and cromolyn on the bronchoconstrictive properties of PGF2alpha. Increasing doses of aerosolized PGF2alpha were given (150, 300, 600, 1200 microgram) and the response of subjects was determined by measurements of spirometry, specific airway conductance (SGaw), and closing volumes. In normal subjects, PGF2alpha induced small but significant decreases of SGaw and spirometric parameters (FVC, FEV1), whereas there was no effect on the closing volumes. In contrast, in asthmatics, PGF2 alpha induced large decreases of SGaw and spirometric parameters. Asthmatics experienced severe and prolonged shortness of breath and wheezing, whereas normal controls experienced neither. Neither atropine nor atropine plus cromolyn was capable of preventing or substantially reversing the PGF2alpha-induced symptoms and airway constriction. The data suggest that reflex bronchoconstriction via irritant receptors is not a major mechanism of PGF2alpha-induced airway constriction. Although a minor vagally mediated reflex component may participate in the PGF2alpha-induced bronchoconstriction, it is masked by an overwhelming non-reflex mechanism that is probably a direct constricting effect of airways smooth muscle that is exquisitely sensitive to PGF2alpha.
D000293:Adolescent; D000328:Adult; D000403:Airway Resistance; D001249:Asthma / Q000503:physiopathology; D001285:Atropine / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects / Q000294:innervation; D001986:Bronchial Spasm / Q000139:chemically induced*; D004205:Cromolyn Sodium / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008176:Lung Volume Measurements; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011460:Prostaglandins F / Q000009:adverse effects*; D012018:Reflex; D013147:Spirometry
D011460:Prostaglandins F; D001285:Atropine; D004205:Cromolyn Sodium