PHARMACOLOGICAL MODIFICATION OF PULMONARY VASCULAR INJURY - POSSIBLE ROLE OF CAMP
PHARMACOLOGICAL MODIFICATION OF PULMONARY VASCULAR INJURY - POSSIBLE ROLE OF CAMP
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DOI：
10.1152/jappl.1987.62.1.47
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发表时间：
1987-01-01
影响因子：
3.3
通讯作者：
MICHAEL, JR
中科院分区：
文献类型：
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作者：
FARRUKH, IS;GURTNER, GH;MICHAEL, JR
在离体兔肺灌注Krebs-Henseleit缓冲液后，用增加肺内腺苷3“，5”-环一磷酸（cAMP）的药物，可预防氧化剂过氧化脂质叔丁基氢过氧化物（t-bu-OOH）引起的肺动脉高压和血管通透性增加。还研究了用吲哚美辛或维拉帕米进行的预处理，因为这些药物阻断了由t-bu-OOH引起的肺动脉压升高。吲哚美辛或维拉帕米可防止肺动脉高压，但不能防止t-bu-OOH引起的通透性增加。因此，吲哚美辛或维拉帕米治疗部分减少了t-bu-OOH引起的肺重量增加。相反，用异丙肾上腺素、前列腺素E1或cAMP类似物预处理不仅可以预防肺动脉高压，而且还可以抑制由t-bu-OOH引起的血管通透性增加。因此，这些药物完全阻断了t-bu-OOH引起的肺重量增加。用氨茶碱或cAMP类似物后处理也显著降低了由t-bu-OOH引起的肺重量增加。这些结果表明，药物治疗可以减少肺动脉高压和增加血管通透性所造成的输液的脂质过氧化氢。由于异丙肾上腺素，氨茶碱，前列腺素E1，和cAMP类似物都有类似的效果，结果表明，其保护作用的可能共同机制是增加cAMP。
Experiments were designed to test the hypothesis that drugs which increase adenosine 3'',5''-cyclic monophosphate (cAMP) in the lung would prevent the pulmonary hypertension and the increase in vascular permeability caused by the infusion of the oxidant lipid peroxide, tert-butyl hydroperoxide (t-bu-OOH), in isolated rabbit lungs perfused with Krebs-Henseleit buffer. Pretreatment with indomethacin or verapamil was also studied, since these drugs block the increase in pulmonary arterial pressure caused by t-bu-OOH. Indomethacin or verapamil prevented the pulmonary hypertension but did not prevent the increase in permeability caused by t-bu-OOH. Consequently, indomethacin or verapamil treatment partially reduced the gain in lung weight caused by t-bu-OOH. In contrast, pretreatment with isoproterenol, prostaglandin E1, or a cAMP analogue not only prevented the pulmonary hypertension but also inhibited the increase in vascular permeability caused by t-bu-OOH. Consequently, these drugs completely blocked the gain in lung weight caused by t-bu-OOH. Posttreatment with aminophylline or the cAMP analogue also significantly reduced the gain in lung weight caused by t-bu-OOH. These results indicate that pharmacological therapy can reduce the pulmonary hypertension and the increase in vascular permeability caused by the infusion of a lipid hydroperoxide. Since isoproterenol, aminophylline, prostaglandin E1, and a cAMP analogue all had similar effects, the results suggest that the likely common mechanism for their protective effect is an increase in cAMP.