在麻醉犬中，别嘌醇和氨氯地平可改善心肌缺血再灌注后的冠状动脉血管舒张功能。

Allopurinol and amlodipine improve coronary vasodilatation after myocardial ischaemia and reperfusion in anaesthetized dogs.

作者信息

Sobey C G, Dalipram R A, Woodman O L

机构信息

Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.

出版信息

Br J Pharmacol. 1993 Feb;108(2):342-7. doi: 10.1111/j.1476-5381.1993.tb12807.x.

DOI:10.1111/j.1476-5381.1993.tb12807.x

PMID:8448585

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1907964/

Abstract

We have assessed the effect of allopurinol, amlodipine and propranolol pretreatment on both endothelium-dependent and endothelium-independent coronary vasodilatation in vivo, by comparing pre-ischaemic responses with those measured after 60 min of coronary artery occlusion and 30 min of reperfusion in anaesthetized dogs. 2. In 15 untreated dogs ischaemia and reperfusion attenuated the increases in coronary blood flow produced by either acetylcholine (0.01-0.05 micrograms kg-1, i.a.) or glyceryl trinitrate (0.05-0.2 micrograms kg-1, i.a.), to an average of 39 +/- 4% and 42 +/- 5% of the pre-ischaemic control response, respectively (both P < 0.05). 3. In 5 dogs treated with allopurinol (25 mg kg-1, orally, 24 h previously, plus 50 mg kg-1, i.v., 5 min before occlusion), the increases in coronary blood flow after ischaemia and reperfusion (acetylcholine: 78 +/- 12%, glyceryl trinitrate: 60 +/- 3% of pre-ischaemic response) were significantly larger than post-ischaemic responses in untreated dogs (both P < 0.05). 4. Similarly, amlodipine treatment (3 micrograms kg-1 min-1, i.v., starting 90 min before occlusion) in 5 dogs improved post-ischaemic increases in blood flow (acetylcholine: 58.5%, glyceryl trinitrate: 66 +/- 6% of pre-ischaemic response, significantly greater than post-ischaemic responses in untreated dogs, P < 0.05). 5. In contrast, in a further 6 dogs pretreated with propranolol (1 mg kg-1, i.v., 30 min before occlusion,plus 0.5 mg kg-1 h-1, i.v.), blood flow responses after ischaemia and reperfusion were not different from post-ischaemic responses in untreated dogs (acetylcholine: 46 +/- 6%, glyceryl trinitrate: 46 +/-6% of pre-ischaemic response).6. These results suggest that allopurinol and amlodipine protect against the post-ischaemic impairment of endothelium-dependent and endothelium-independent coronary vasodilatation in vivo by mechanisms additional to endothelial protection.

摘要

我们通过比较麻醉犬冠状动脉闭塞60分钟及再灌注30分钟后与缺血前的反应，评估了别嘌醇、氨氯地平和普萘洛尔预处理对体内内皮依赖性和非内皮依赖性冠状动脉血管舒张的影响。2. 在15只未经处理的犬中，缺血和再灌注使乙酰胆碱（0.01 - 0.05微克/千克，动脉内注射）或硝酸甘油（0.05 - 0.2微克/千克，动脉内注射）所引起的冠状动脉血流增加分别减弱至缺血前对照反应的平均39±4%和42±5%（均P < 0.05）。3. 在5只接受别嘌醇治疗的犬中（25毫克/千克，口服，提前24小时，加50毫克/千克，静脉注射，闭塞前5分钟），缺血和再灌注后的冠状动脉血流增加（乙酰胆碱：缺血前反应的78±12%，硝酸甘油：60±3%）显著大于未经处理犬的缺血后反应（均P < 0.05）。4. 同样，5只犬接受氨氯地平治疗（3微克/千克·分钟，静脉注射，闭塞前90分钟开始）后，缺血后血流增加（乙酰胆碱：缺血前反应的58.5%，硝酸甘油：66±[此处原文似乎有误，多了一个“+”号，若按6%计算]6%）显著大于未经处理犬的缺血后反应（P < 0.05）。5. 相比之下，在另外6只预先用普萘洛尔处理的犬中（1毫克/千克，静脉注射，闭塞前30分钟，加0.5毫克/千克·小时，静脉注射），缺血和再灌注后的血流反应与未经处理犬的缺血后反应无差异（乙酰胆碱：缺血前反应的46±6%，硝酸甘油：46±6%）。6. 这些结果表明，别嘌醇和氨氯地平通过内皮保护以外的机制，预防体内缺血后内皮依赖性和非内皮依赖性冠状动脉血管舒张的损伤。