Pethö A, Neumann T, Vetterlein F, Schmidt G
Zentrum Pharmakologie und Toxikologie, Georg-August-Universität Göttingen, Federal Republic of Germany.
Microvasc Res. 1989 Nov;38(3):223-36. doi: 10.1016/0026-2862(89)90001-0.
Renal microcirculation and function were studied in the unilateral clamp-induced ischemia/reperfusion model in anesthetized rats. After 60-min reperfusion fluorochromelabeled globulin was injected i.v. allowing histological determination of capillary plasma flow patterns (CPFP). In the 60-min ischemia protocol the untreated group revealed poor capillary labeling in the outer medulla (OM), whereas cortical perfusion patterns were only slightly altered. Pre- and postischemic treatment with diltiazem led to significant improvement of CPFP in the OM: 4.9% of tissue areas were lying more than 60 microns from the next perfused capillary vs 70.2% after untreated ischemia. Postischemic treatment with diltiazem proved much less effective. Inulin clearance (CIn) amounted to less than 2% of baseline values irrespective of the treatment regimen. However, in the 30-min ischemia protocol, displaying normal CPFP, preservation of CIn was evident and most effective after pre- and postischemic diltiazem treatment (53% vs 8% after untreated ischemia). Measurements of tubular function, however, did not reveal any significant improvement after diltiazem treatment. This observation and the fact that the drugs has a vasodilating effect lend support to the view that the preservation of glomerular filtration rate (GFR) is most likely mediated by vascular mechanisms. In conclusion, in this experimental model diltiazem significantly reduced postischemic disturbances of renal microcirculation occurring after prolonged periods of ischemia and was clearly efficient in maintaining GFR after shorter ischemic episodes; however, tubular function was not preserved. Our results, as well as those of other authors, strongly suggest that diltiazem causes the aforementioned effects mainly by actions at the vascular site.
在麻醉大鼠的单侧夹闭诱导缺血/再灌注模型中研究了肾微循环和功能。再灌注60分钟后，静脉注射荧光素标记的球蛋白，以便通过组织学方法确定毛细血管血浆流动模式（CPFP）。在60分钟缺血方案中，未治疗组在外髓质（OM）中显示出较差的毛细血管标记，而皮质灌注模式仅略有改变。缺血前后用硫氮䓬酮治疗可显著改善OM中的CPFP：4.9%的组织区域距离下一个灌注毛细血管超过60微米，而未治疗的缺血组为70.2%。硫氮䓬酮缺血后治疗效果差得多。无论治疗方案如何，菊粉清除率（CIn）均低于基线值的2%。然而，在30分钟缺血方案中，CPFP正常，硫氮䓬酮缺血前后治疗后CIn的保留明显且最有效（53% vs未治疗缺血后的8%）。然而，硫氮䓬酮治疗后肾小管功能测量未显示任何显著改善。这一观察结果以及该药物具有血管舒张作用这一事实支持了肾小球滤过率（GFR）的保留最可能由血管机制介导的观点。总之，在该实验模型中，硫氮䓬酮显著减少了长时间缺血后发生的缺血后肾微循环紊乱，并且在较短缺血发作后明显有效地维持了GFR；然而，肾小管功能未得到保留。我们的结果以及其他作者的结果强烈表明，硫氮䓬酮主要通过作用于血管部位引起上述效应。
