Clinical, functional and pathogenetic aspects of bronchial reactivity to prostaglandins F2alpha, E1, and E2.
Based on our results and on those reported in literature, we may draw the following conclusions. As a rule, asthmatic patients are markedly more sensitive than normal subjects to the bronchoconstrictive action of PGF2alpha by aerosol. However, the individual response is quite variable, which predicts and justifies some exceptions. On this subject, we found a peculiar exception in a female patient with extrinsic asthma, who tolerated abnormally large amounts of PGF2alpha. In contrast, we found a normal subject, who developed a bronchial hypersensitivity to PGF2alpha of frankly asthmatic type, following a moderate postinfluenzal bronchitis. Intravenously PGF2alpha loses the most part of its bronchoconstrictive effect, probably because it is rapidly metabolized before it may reach the bronchial receptors involved in the bronchospastic response. On the contrary, the action on vascular smooth muscle of the pulmonary circulation is evident, just because it is reached before the above transformation, mainly performed by 15-PG-dehydrogenase. An important component of the PGF2alpha-induced bronchospasm, although varying individually, is surely nonspecific, as it is shown by the protection obtained with an atropine-like agent. The moderate but significant protection obtained with DSCG, may be interpreted in a way similar to the one exerted again by DSCG on other nonspecific stimuli. Since indoramine has no effect in preventing PGF2alpha-induced bronchospasm, the intervention of bronchial alpha-receptors in the pathogenesis of this type of bronchospasm may be excluded. Nonsteroid antiinflammatory agents do not seem to change in asthmatic patients bronchial reactivity to PGF2alpha, as was found recently with other specific and nonspecific stimuli. Our studies do not modify current thought regarding the poor present therapeutic value of PGE as bronchodilator agents. Prospects are no better with the stereoisomer of PGF2alpha, PGF2beta (41), with endoperoxides PGG2 and PGH2 (42) and with the analogues 15-methyl-PGE2, 15-epi-PGA2, and 8-iso-PGE1 (43). However, it is reassuring that, even in the absence of a demonstrable bronchodilator effect, both PGE1 and PGE2 are capable to prevent in a large degree the specifically and nonspecifically induced bronchospasm.
D000328:Adult; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001986:Bronchial Spasm / Q000139:chemically induced / Q000188:drug therapy; D001991:Bronchitis / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004205:Cromolyn Sodium / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use; D007217:Indoramin / Q000627:therapeutic use; D007275:Injections, Intravenous; D009241:Ipratropium / Q000627:therapeutic use; D008297:Male; D011458:Prostaglandins E / Q000627:therapeutic use*; D011460:Prostaglandins F / Q000494:pharmacology / Q000627:therapeutic use*; D011652:Pulmonary Circulation / Q000187:drug effects
D000336:Aerosols; D000485:Allergens; D011458:Prostaglandins E; D011460:Prostaglandins F; D007217:Indoramin; D009241:Ipratropium; D004205:Cromolyn Sodium; D007213:Indomethacin