Zakaria El Rasheid, Hunt C Michelle, Li Na, Harris Patrick D, Garrison R Neal
Department of Physiology and Biophysics, Health Sciences Center A-1115, University of Louisville, Louisville, KY 40292, USA.
J Am Soc Nephrol. 2005 Oct;16(10):2931-40. doi: 10.1681/ASN.2004090764. Epub 2005 Aug 3.
Conventional peritoneal dialysis solutions (PDS) are vasoactive. This study was conducted to identify vasoactive components of PDS and to describe quantitatively such vasoactivity. Anesthetized nonheparinized rats were monitored continuously for hemodynamics while the microvasculature of the jejunum was studied with in vivo intravital microscopy. In separate experiments, vascular reactivity of rat endothelium-intact and -denuded aortic rings (2 mm) was studied ex vivo in a standard tissue bath. In both studies, suffusion of the vessels was performed with filter-sterilized isotonic and hypertonic solutions that contained glucose or mannitol as osmotic agents. PDS served as a control (Delflex 2.25%). Hypertonic glucose and mannitol solutions produced a significant vascular reactivity in aortic rings and instantaneous and sustained vascular relaxation at all levels of the intestinal microvasculature. Similarly, lactate that was dissolved in a low-pH isotonic physiologic salt solution produced significant force generation in aortic rings. Whereas isotonic glucose and mannitol solutions had no vasoactivity in aortic rings, isotonic glucose produced a selective, insidious, and time-dependent vasodilation in the intestinal premucosal arterioles (18 +/- 0.2% of baseline), which was not observed in the larger inflow arterioles (100 mum). This isotonic glucose-mediated vascular relaxation can be attenuated by approximately 50% with combined adenosine A(2a) and A(2b) receptor antagonists and completely abolished by adenosine A(1) receptor inhibition. By using two different experimental techniques, this study demonstrates that hyperosmolality and lactate are the major vasoactive components of clinical peritoneal dialysis solutions. The pattern and the magnitude of such reactivity are dependent on vessel size and on the solutes' metabolic activity. Low pH of conventional PDS is not a vasoactive component by itself but renders lactate vasoactive. Energy-dependent transport of glucose into cells mediates vasodilation of small visceral arterioles by an adenosine receptor-mediated mechanism and constitutes a significant fraction of PDS-mediated vascular reactivity in the visceral microvasculature.
传统的腹膜透析液（PDS）具有血管活性。本研究旨在确定PDS的血管活性成分并定量描述这种血管活性。对麻醉且未肝素化的大鼠进行连续血流动力学监测，同时用体内活体显微镜研究空肠的微血管。在单独的实验中，在标准组织浴中离体研究大鼠内皮完整和去内皮的主动脉环（2毫米）的血管反应性。在两项研究中，用含有葡萄糖或甘露醇作为渗透剂的滤过除菌等渗和高渗溶液灌注血管。PDS用作对照（Delflex 2.25%）。高渗葡萄糖和甘露醇溶液在主动脉环中产生显著的血管反应性，并在肠道微血管的各个水平产生瞬时和持续的血管舒张。同样，溶解在低pH等渗生理盐溶液中的乳酸在主动脉环中产生显著的力量产生。而异渗葡萄糖和甘露醇溶液在主动脉环中无血管活性，异渗葡萄糖在肠道黏膜前小动脉中产生选择性、隐匿性和时间依赖性血管舒张（为基线的18±0.2%），在较大的流入小动脉（100μm）中未观察到。这种异渗葡萄糖介导的血管舒张可被腺苷A(2a)和A(2b)受体拮抗剂联合使用减弱约50%，并被腺苷A(1)受体抑制完全消除。通过使用两种不同的实验技术，本研究表明高渗和乳酸是临床腹膜透析液的主要血管活性成分。这种反应性的模式和程度取决于血管大小和溶质的代谢活性。传统PDS的低pH本身不是血管活性成分，但可使乳酸具有血管活性。葡萄糖向细胞的能量依赖性转运通过腺苷受体介导的机制介导小内脏小动脉的血管舒张，并构成PDS在内脏微血管中介导的血管反应性的很大一部分。
