Pasargiklian M, Bianco S, Allegra L
Adv Prostaglandin Thromboxane Res. 1976;1:461-75.
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.
基于我们的研究结果以及文献中所报道的结果，我们可以得出以下结论。通常情况下，哮喘患者通过气雾剂对PGF2α的支气管收缩作用比正常受试者明显更敏感。然而，个体反应差异很大，这预示并解释了一些例外情况。关于这一点，我们在一名患有外源性哮喘的女性患者身上发现了一个特殊的例外，她能耐受异常大量的PGF2α。相反，我们发现一名正常受试者在中度流感后支气管炎后，对PGF2α产生了明显哮喘类型的支气管超敏反应。静脉注射PGF2α大部分支气管收缩作用丧失，可能是因为它在到达参与支气管痉挛反应的支气管受体之前就迅速被代谢了。相反，它对肺循环血管平滑肌的作用很明显，这正是因为在上述转化（主要由15 - PG -脱氢酶进行）之前它就到达了血管平滑肌。PGF2α诱导的支气管痉挛的一个重要组成部分，尽管个体有所不同，但肯定是非特异性的，这一点从用类似阿托品的药物所获得的保护作用中可以看出。用色甘酸钠（DSCG）获得的适度但显著的保护作用，可以用与DSCG对其他非特异性刺激所发挥的作用类似的方式来解释。由于吲哚胺在预防PGF2α诱导的支气管痉挛方面没有作用，因此可以排除支气管α受体在这类支气管痉挛发病机制中的干预作用。非甾体抗炎药似乎不会改变哮喘患者对PGF2α的支气管反应性，最近对其他特异性和非特异性刺激的研究也发现了同样的情况。我们的研究并没有改变目前关于PGE作为支气管扩张剂治疗价值不大的观点。PGF2α的立体异构体PGF2β（41）、内过氧化物PGG2和PGH2（42）以及类似物15 -甲基 - PGE2、15 -表 - PGA2和8 -异 - PGE1（43）的前景也没有更好。然而，令人放心的是，即使没有明显的支气管扩张作用，PGE1和PGE2在很大程度上都能够预防特异性和非特异性诱导的支气管痉挛。
