Nakada T, Iijima Y, Kubota Y, Watanabe M, Ishigooka M, Suzuki H
Department of Urology, Yamagata University, School of Medicine, Japan.
J Urol. 1996 Sep;156(3):1180-5.
Although the enhanced renin-angiotensin (R-A) system responsible for two-kidney, one-clip (2K-1C) hypertension is well known, there may be a shift with time so that this, hemodynamic factor plays a less important role and increased vascular resistance is predominant in sustaining hypertension. While increased vascular protein synthesis has been demonstrated in genetically hypertensive rats, we evaluated the possible relationship between vascular protein synthesis and 2K-1C hypertension with special reference to the R-A system.
Two-kidney one-clip rats were treated with splanchnicotomy, beta-aminopropionitrile (collagen inhibitor), or captopril (angiotensin converting enzyme inhibitor) in the acute or chronic hypertensive phase. 3H-proline was injected into rats, and incorporation rates of 3H-proline into vascular collagen, noncollagenous protein and elastin were counted. The plasma level of the R-A system was assayed.
In the acute phase of 2K-1C hypertensive rats whose R-A system was enhanced, captopril treatment further enhanced plasma renin activity and plasma angiotensin I and suppressed plasma angiotensin II while reducing blood pressure. Synthesis of the vascular proteins was almost identical. In the chronic phase of 2K-1C hypertensive rats whose R-A system was within normal limits, increased incorporation rates of 3H-proline into noncollagenous protein or collagen of mesenteric arteries were decreased by splanchnicotomy or beta-aminopropionitrile and hypertension was lowered. Captopril failed to reduce protein synthesis.
An enhanced R-A system participates in the pathogenesis of the acute phase of 2K-1C hypertension while increased noncollagenous protein and collagen syntheses of small arteries appear to play some role in the etiology of the chronic phase of hypertension.
虽然导致二肾一夹（2K-1C）高血压的肾素-血管紧张素（R-A）系统增强已为人所知，但随着时间推移可能会发生变化，使得这种血流动力学因素的作用减弱，而血管阻力增加在维持高血压中起主要作用。虽然在遗传性高血压大鼠中已证实血管蛋白合成增加，但我们评估了血管蛋白合成与2K-1C高血压之间的可能关系，并特别参考了R-A系统。
在急性或慢性高血压期，对二肾一夹大鼠进行内脏神经切断术、β-氨基丙腈（胶原抑制剂）或卡托普利（血管紧张素转换酶抑制剂）治疗。将3H-脯氨酸注入大鼠体内，计算3H-脯氨酸掺入血管胶原、非胶原蛋白和弹性蛋白的速率。测定R-A系统的血浆水平。
在R-A系统增强的2K-1C高血压大鼠急性期，卡托普利治疗进一步提高了血浆肾素活性和血浆血管紧张素I水平，抑制了血浆血管紧张素II水平，同时降低了血压。血管蛋白的合成几乎相同。在R-A系统处于正常范围的2K-1C高血压大鼠慢性期，内脏神经切断术或β-氨基丙腈可降低3H-脯氨酸掺入肠系膜动脉非胶原蛋白或胶原的速率增加，血压降低。卡托普利未能降低蛋白合成。
增强的R-A系统参与2K-1C高血压急性期的发病机制，而小动脉非胶原蛋白和胶原合成增加似乎在高血压慢性期的病因中起一定作用。
