Induction of bronchial hypersensitivity: evidence for a role for prostaglandins.
Bronchial hyper-responsiveness is a particular feature of asthma, but also occurs in normal subjects after a viral upper respiratory tract infection or ozone inhalation. Such stimuli would be expected to result in the release of chemical mediators of inflammation. In this study, the effects of one of these, prostaglandin F2 alpha (PGF2 alpha), on the response of normal subjects to inhaled histamine has been investigated. Nine normal volunteers took 10 inhalations of increasing concentrations of PGF2 alpha at 15-minute intervals from a Wright's nebuliser under standard conditions until a change in sGaw could be detected. The next lowest serial dilution of PGF2 alpha was subsequently inhaled by each subject every 15 min for 90 min to ensure the absence of a cumulative effect. Inhalation dose-response curves to histamine diphosphate were constructed on two separate occasions using the same standardised technique. Doses were administered every 15 min and sGaw determined five minutes after each. On one occasion each dose of histamine was immediately preceded by the non-active test dose of PGF2 alpha and on the second by saline as placebo. The study was performed double-blind and in random order. After pretreatment with PGF2 alpha the histamine dose-response curve was significantly shifted to the left in a parallel fashion (p less than 0.001). There was a significant decrease in the doses of histamine required to cause a 20% fall in sGaw (p less than 0.0015) but no significant change in the slopes of the dose-response regression lines, indicating that bronchial muscle sensitivity rather than reactivity had been predominantly affected.
D000328:Adult; D001980:Bronchi / Q000187:drug effects*; D001985:Bronchial Provocation Tests; D015237:Dinoprost; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects; D011460:Prostaglandins F / Q000494:pharmacology*
D011460:Prostaglandins F; D006632:Histamine; D015237:Dinoprost