Pathogenesis of renovascular hypertension with special reference to vascular protein synthesis

两肾一夹(2K-1C)大鼠在高血压急性期或慢性高血压期分别给予Splan切开术、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。给大鼠注射3 H-Pro，计数3 H-Pro对血管胶原、非胶原蛋白和弹性蛋白的掺入。测定血浆肾素-血管紧张素系统(R-A)水平。在R-A系统增强的2K-1C高血压大鼠急性期，卡托普利在降低血压的同时进一步升高PRA和血管紧张素I，抑制血管紧张素II。在R-A系统正常的2K-1C高血压大鼠慢性期，内脏切开或β-氨基丙腈可降低~3H-Pro掺入肠系膜动脉非胶原蛋白或胶原的比率，从而降低高血压。卡托普利未能降低PRO…更多的蛋白质合成。因此，增强的R-A系统参与了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的增加似乎在慢性期高血压的病因中起到了一定作用。在另一项实验中，高水平的多巴胺(DA)、DPAC和HVA等单胺类物质增强了交感神经系统，导致2K-1C急性期高血压，而2K-1C慢性期高血压。临床研究分析了99例肾血管性高血压患者。结果表明：(1)对于纤维肌肉发育不良和大动脉炎患者，治愈患者的平均年龄比未治愈患者年轻，且前者的术前高血压病程短于后者，但对于动脉粥样硬化症患者，这些指标在治愈、缓解和未治愈组之间无显著差异；(2)对于受累的肾动脉，双侧肾动脉和主动脉的病变或位于肾外和肾内动脉的病变在任何组织学形式下都难以治愈；(3)对于纤维肌肉发育不良患者，高血压的改善比动脉粥样硬化者更多。直立体位试验的结果与此相似，但对大动脉炎患者几乎没有作用。这些结果表明，增强的R-A系统对纤维肌肉发育不良和动脉粥样硬化患者的高血压维持仍有一定的作用，但对于术前高血压病程较长的大动脉患者，必须考虑其他导致高血压维持的因素。较少

Two-kidney-one, one-clip (2K-1C) rats were treated with splan-chnicotomy, 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 of 3H-proline into vascular collagen, non-collagenous protein and elastin were counted. The plasma level of the renin-angiotensin (R-A) system was assayed. In the acute phase of 2K-1C hypertensive rats whose R-A system was enhanced, captopril treatment further enhanced PRA and angiotensin I and suppressed angiotensin II while reducing blood pressure. Synthesis of the vascular protein 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 non-collagenous protein or collagen of mesenteric arteries were decreased by splanchnicotomy or beta-aminopropionitrile and hypertension was lowered. Captopril failed to reduce pro … More tein synthesis. Thus, an enhanced R-A system participates in the pathogenesis of the acute phase of 2K-1C hypertension while increased non-collagenous protein and collagen syntheses of small arteries appear to play some role in the etiology of chronic phase of hypertension. In another experiment, high level of monoamines, such as dopamine (DA), DPAC and HVA enhanced synpathetic nerve system which resulted in hypertension in acute phase of 2K-1C, but not in chronic phase of 2K-1C.In clinical study we analyzed 99 patients with renovascular hypertension. Evidence has been presented that : (1) for patients with fibromuscular dysplasia and those with aortitis the mean age of cured patients was younger than non-cured patients and the preoperative hypertensive period of the former patients was shorter than the latter patients, but as for the patients with atherosclerosis, there were no significant differences in these variables among cured, alleviative and non-cured groups, (2) for the affected renal arteries, lesions of bilateral renal artery and aorta or lesions located at extrarenal and intrarenal arteries were difficult to be cured in any histological vascular forms, (3) for the patients with fibromuscular dysplasia, improvement of hypertension was achieved more frequently than those with atherosclerosclerosis. Similar result was obtained in the upright posture test in lesser extent, but a almost useless in patients with aortitis.These results indicate that enhenced R-A system still appears to play some role for sustaining hypertension in patients with fibromuscular dysplasia and those with atherosclerosis, but other factors responsible for maintenance of hypertension must be considered in patients with aortitits whose preoperative hypertensive period is long. Less