Plante G E, Bissonnette M, Sirois M G, Regoli D, Sirois P
Department of Medicine, University of Sherbrooke, Québec, Canada.
J Clin Invest. 1992 Jun;89(6):2030-2. doi: 10.1172/JCI115813.
Vascular permeability disorders have been described in experimental models, as well as in human hypertension. We recently described the fact that vascular permeability to albumin is heterogeneous in the normal rat. In the present study, we examine the contents of Evans blue dye (EB) bound to albumin in selected organs of unanesthetized Wistar Kyoto (WKY) and in spontaneously hypertensive rats (SHR) at various stages of development of hypertension. EB was injected in the caudal vein of paired 4, 8, 12, and 16-wk-old WKY and SHR. Rats were killed 10 min after EB injection and extraction of the marker was measured in selected tissues. In additional 4 and 16-wk-old animals, bradykinin B1 and B2 receptor antagonists (BKA) were also injected with EB. Renal contents of EB bound to albumin were higher in the SHR than in the WKY: 196 +/- 9, 202 +/- 10, 182 +/- 7, and 196 +/- 9, compared with 158 +/- 8, 155 +/- 7, 138 +/- 7, and 118 +/- 6 micrograms/g dry tissue, in the 4, 8, 12, and 16-wk-old rats, respectively. In the 4-wk-old SHR and WKY, blood pressure values were normal and comparable, yet the alteration in EB permeability was already present in the SHR. Both BKA failed to alter the renal EB extravasation in the WKY, but the B2-BKA restored the renal permeability to control levels in the SHR. We conclude that a selective defect in the renal vascular permeability to EB developed in the SHR. Since this finding precedes hypertension and is corrected by a selective B2-BKA, it is suggested that bradykinin is involved at an early stage of the disease in the SHR.
血管通透性障碍在实验模型以及人类高血压中均有描述。我们最近发现，正常大鼠血管对白蛋白的通透性是不均一的。在本研究中，我们检测了未麻醉的Wistar Kyoto（WKY）大鼠和自发性高血压大鼠（SHR）在高血压发展的不同阶段，选定器官中与白蛋白结合的伊文思蓝染料（EB）含量。将EB注入4、8、12和16周龄配对的WKY大鼠和SHR的尾静脉。注射EB后10分钟处死大鼠，并在选定组织中测量标志物的提取量。在另外的4周龄和16周龄动物中，还将缓激肽B1和B2受体拮抗剂（BKA）与EB一起注射。与WKY大鼠相比，SHR大鼠肾脏中与白蛋白结合的EB含量更高：在4、8、12和16周龄大鼠中，分别为196±9、202±10、182±7和196±9微克/克干组织，而WKY大鼠分别为158±8、155±7、138±7和118±6微克/克干组织。在4周龄的SHR和WKY大鼠中，血压值正常且相当，但SHR大鼠中EB通透性的改变已经存在。两种BKA均未改变WKY大鼠肾脏的EB外渗，但B2-BKA可将SHR大鼠的肾脏通透性恢复至对照水平。我们得出结论，SHR大鼠出现了肾脏血管对EB通透性的选择性缺陷。由于这一发现先于高血压出现，且可被选择性B2-BKA纠正，因此提示缓激肽在SHR大鼠疾病的早期阶段起作用。
