Laragh J H
Cardiovascular Center, New York Hospital-Cornell Medical Center, New York, New York 10021.
Am J Med. 1989 Dec 26;87(6B):2S-14S. doi: 10.1016/0002-9343(89)90084-3.
It is proposed that in essential hypertension there are two functionally abnormal populations of nephrons. One is ischemic; chronically hypersecreting renin and underexcreting sodium. The other, the larger population, is in adaptive hypernatriuresis with its renin secretion chronically suppressed. Nephrons in these two populations, each with its own detector-effector apparatus for renin secretion and sodium excretion, behave according to their individual needs, producing a physiologic discordance expressed in high blood pressure even with plasma renin levels in the so-called "normal" range. The unsuppressed and inappropriate renin secretion from the ischemic nephrons impairs renal function in ischemic and hyperfiltering nephrons alike, but in very different ways. To maintain glomerular filtration rate and an adequate excretion of sodium, the ischemic nephrons require a higher rate of renin secretion than they are actually receiving, because at low perfusion pressures maximal angiotensin II-induced efferent arteriolar constriction is needed to maintain glomerular filtration rate. On the other hand, the compensating hypernatriuretic nephrons become unable fully to excrete dietary sodium because they are exposed to an unwanted, inappropriately high angiotensin II level coming from the ischemic nephrons. This angiotensin II impairs sodium excretion (adaptive hypernatriuresis) from unaffected, adapting nephrons by promoting proximal sodium reabsorption and by inducing afferent constriction. The net result is that all nephrons are exposed to angiotensin II levels inappropriate for their needs. This leads to impaired ability to excrete sodium by both populations of nephrons, with sodium retention in the presence of abnormal renin secretion and perpetuation of the hypertension. The hypothesis is consistent with the hallmark pathology of multifocal afferent arteriolar narrowing seen in essential hypertension as well as with the characteristic renal hemodynamic pattern of vasoconstriction with reduced renal blood flow but with maintained glomerular filtration rate. The "normal" glomerular filtration rate as well as the often "normal" plasma renin activity may be seen as the sum of effects on the two abnormally acting populations of nephrons. Further, since any circulating renin is inappropriate in the presence of hypertension, the hypothesis helps explain why angiotensin-converting enzyme inhibitors reduce blood pressure even when renin levels are not elevated.
有人提出，在原发性高血压中存在两种功能异常的肾单位群体。一种是缺血性的；长期分泌过多肾素且钠排泄不足。另一种，也是数量较多的群体，处于适应性高钠尿状态，其肾素分泌长期受到抑制。这两种群体中的肾单位，各自具有用于肾素分泌和钠排泄的自身检测 - 效应器装置，根据其个体需求发挥作用，即使血浆肾素水平处于所谓的“正常”范围，也会产生以高血压为表现的生理失调。缺血性肾单位未受抑制且不适当的肾素分泌会损害缺血性和高滤过性肾单位的肾功能，但方式非常不同。为了维持肾小球滤过率和足够的钠排泄，缺血性肾单位需要比实际接受的更高的肾素分泌速率，因为在低灌注压力下，需要最大程度的血管紧张素 II 诱导的出球小动脉收缩来维持肾小球滤过率。另一方面，代偿性高钠尿性肾单位无法完全排泄饮食中的钠，因为它们暴露于来自缺血性肾单位的不必要的、不适当的高血管紧张素 II 水平。这种血管紧张素 II 通过促进近端钠重吸收和诱导入球小动脉收缩，损害未受影响的适应性肾单位的钠排泄（适应性高钠尿）。最终结果是所有肾单位都暴露于与其需求不匹配的血管紧张素 II 水平。这导致两种肾单位群体的钠排泄能力受损，在肾素分泌异常的情况下出现钠潴留，并使高血压持续存在。该假说与原发性高血压中所见的多灶性入球小动脉狭窄的标志性病理以及肾血管收缩、肾血流量减少但肾小球滤过率维持的特征性肾血流动力学模式一致。“正常”的肾小球滤过率以及通常“正常”的血浆肾素活性可能被视为对两种异常作用的肾单位群体影响的总和。此外，由于在高血压存在的情况下任何循环肾素都是不适当的，该假说有助于解释为什么即使肾素水平未升高，血管紧张素转换酶抑制剂也能降低血压。
