血管紧张素转换酶抑制剂会增强豚鼠体内由P物质诱导的支气管收缩作用。

Angiotensin converting enzyme inhibitors potentiate the bronchoconstriction induced by substance P in the guinea-pig.

作者信息

Subissi A, Guelfi M, Criscuoli M

机构信息

Department of Pharmacology, Laboratori Guidotti S.p.A., Pisa, Italy.

出版信息

Br J Pharmacol. 1990 Jul;100(3):502-6. doi: 10.1111/j.1476-5381.1990.tb15837.x.

DOI:10.1111/j.1476-5381.1990.tb15837.x

PMID:1697196

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1917780/

Abstract

The effects of intravenous captopril and enalaprilic acid on the increase in pulmonary inflation pressure induced by different bronchoconstrictor agents were evaluated in the anaesthetized guinea-pig. 2. Captopril and enalaprilic acid (1.6-200 micrograms kg-1) enhanced dose-dependently the bronchoconstriction (BC) induced by substance P. The threshold effective dose was 1.6 micrograms kg-1 and maximal potentiation over the control response was more than 400% for both agents. Enalaprilic acid was also assayed for serum and lung angiotensin converting enzyme (ACE) inhibition in anaesthetized guinea-pigs. This drug produced a dose-dependent inhibition of ACE in both tissues, with ED50 s of 7.6 and 9.4 micrograms kg-1, respectively: this inhibitory activity was positively correlated to substance P potentiation. 3. Captopril (8-1000 micrograms kg-1) enhanced dose-dependently the BC induced by capsaicin. The threshold effective dose was 40 micrograms kg-1 and maximal potentiation about 90%. 4. Captopril (200-1000 micrograms kg-1) did not affect BC induced by bradykinin. However, this response was markedly enhanced (about 200%) by captopril 200 micrograms kg-1 in propranolol-pretreated animals. 5. Captopril and enalaprilic acid (200-1000 micrograms kg-1) slightly (20-40%) but significantly enhanced the BC induced by 5-hydroxytryptamine. However, this response was potentiated to the same extent by a dose of prazosin, which produced a degree of hypotension similar to that observed after administration of the ACE inhibitors. 6. In conclusion, ACE inhibitors potentiate the BC induced by substance P and, to a minor extent, that induced by capsaicin in the anaesthetized guinea-pig. Potentiation of substance P is well correlated with ACE inhibition in guinea-pig serum and lungs. These experimental results may offer a mechanistic interpretation of cough and bronchial hyperreactivity observed in patients receiving treatment with ACE inhibitors.

摘要

在麻醉的豚鼠中评估了静脉注射卡托普利和依那普利酸对不同支气管收缩剂所致肺膨胀压升高的影响。2. 卡托普利和依那普利酸（1.6 - 200微克/千克）剂量依赖性地增强了P物质诱导的支气管收缩（BC）。阈有效剂量为1.6微克/千克，两种药物对对照反应的最大增强超过400%。还在麻醉的豚鼠中检测了依那普利酸对血清和肺血管紧张素转换酶（ACE）的抑制作用。该药物在两种组织中均产生剂量依赖性的ACE抑制，ED50分别为7.6和9.4微克/千克：这种抑制活性与P物质增强作用呈正相关。3. 卡托普利（8 - 1000微克/千克）剂量依赖性地增强了辣椒素诱导的BC。阈有效剂量为40微克/千克，最大增强约90%。4. 卡托普利（200 - 1000微克/千克）不影响缓激肽诱导的BC。然而，在普萘洛尔预处理的动物中，200微克/千克的卡托普利可使该反应显著增强（约200%）。5. 卡托普利和依那普利酸（200 - 1000微克/千克）轻微（20 - 40%）但显著增强了5 - 羟色胺诱导的BC。然而，一剂哌唑嗪可使该反应增强到相同程度，哌唑嗪产生的低血压程度与给予ACE抑制剂后观察到的相似。6. 总之，在麻醉的豚鼠中，ACE抑制剂增强了P物质诱导的BC，并在较小程度上增强了辣椒素诱导的BC。P物质的增强作用与豚鼠血清和肺中的ACE抑制密切相关。这些实验结果可能为接受ACE抑制剂治疗的患者中观察到的咳嗽和支气管高反应性提供一种机制解释。