Case D B, Wallace J M, Keim H J, Sealey J E, Laragh J H
Am J Med. 1976 May 31;60(6):825-36. doi: 10.1016/0002-9343(76)90903-7.
Saralasin was infused into 52 untreated hypertensive patients. Immediate, transient pressor responses occurred in 94 per cent followed by a more gradual sustained change in blood pressure reaching an apogee in about 20 minutes. Most (86 per cent) patients with high renin values had sustained depressor responses irrespective of sodium balance. In contrast, during a normal sodium intake, the drug produced a neutral (45 per cent) or mildly pressor (50 per cent) response in patients with normal renin and pressor responses in patients with low renin values. Sodium depletion abolished pressor responses and resulted in depressor responses in 64 per cent of the patients with normal renin values. The pretreatment angiotensin level appeared to determine direction and amplitude of the response to saralasin, since increases and decreases in diastolic pressure exhibited a highly significant relationship to the control renin lever (r = 0.80, p less than 0.001). Above a neutral range of control renin values, from 2 to 7 ng Al/ml/hour, depressor responses were the rule, and below it pressor responses were consistent. Sodium balance also appeared to determine the amplitude of the response. In a subset of patients with similar renin values (range 1.4 to 2.2 ngAl/ml/hour), the induced pressor responses correlated directly with the 24-hour sodium excretion (p less than 0.05). For all patients, the induced pressure change also was related to the rate of sodium excretion (r = 0.53, p less than 0.001). The data suggest that saralasin behaves as a partial competitive agonist of angiotensin II. For this reason, saralasin testing provided only a rough physiologic validation for renin profiling. Thus, depressor responses expose most patients with high renin values. Neutral responses occur in many patients with normal renin and intermediate renin values. But pressor responses occur in subjects with either low or normal renin levels and they may reflect sodium and volume excess associated with a partial or relative absence of renin. Accordingly, due to its partial agonism, saralasin testing under-estimates the renin factor. Hence, the drug cannot be used to identify or exclude renin involvement in the blood pressure in the large majority of hypertensive patients who do not exhibit depressor responses. For them an agent devoid of agonism is required. Moreover, prior sodium depletion as a device to increase the frequency of depressor responses to saralasin does not measure intrinsic renin dependency of the blood pressure but rather the reactivity of the system to sodium depletion.
将沙拉新注入52例未经治疗的高血压患者体内。94%的患者出现即刻、短暂的升压反应，随后血压逐渐持续变化，约20分钟后达到峰值。大多数（86%）肾素值高的患者无论钠平衡情况如何均出现持续的降压反应。相比之下，在正常钠摄入情况下，该药物在肾素正常的患者中产生中性反应（45%）或轻度升压反应（50%），在肾素值低的患者中产生升压反应。钠缺失消除了升压反应，并使64%肾素值正常的患者出现降压反应。治疗前的血管紧张素水平似乎决定了对沙拉新反应的方向和幅度，因为舒张压的升高和降低与对照肾素水平呈高度显著的关系（r = 0.80，p < 0.001）。在对照肾素值2至7 ng Al/ml/小时的中性范围之上，降压反应是常见的，而在此范围之下升压反应是一致的。钠平衡似乎也决定了反应的幅度。在一组肾素值相似（范围为1.4至2.2 ngAl/ml/小时）的患者中，诱导的升压反应与24小时钠排泄直接相关（p < 0.05）。对于所有患者，诱导的压力变化也与钠排泄率相关（r = 0.53，p < 0.001）。数据表明沙拉新表现为血管紧张素II的部分竞争性激动剂。因此，沙拉新试验仅为肾素分析提供了粗略的生理学验证。因此，降压反应揭示了大多数肾素值高的患者。许多肾素正常和肾素值中等的患者出现中性反应。但升压反应出现在肾素水平低或正常的受试者中，它们可能反映了与部分或相对缺乏肾素相关的钠和容量过多。因此，由于其部分激动作用，沙拉新试验低估了肾素因素。因此，在大多数未表现出降压反应的高血压患者中，该药物不能用于识别或排除肾素对血压的影响。对于他们来说，需要一种无激动作用的药物。此外，预先进行钠缺失作为增加对沙拉新降压反应频率的一种手段，测量的不是血压对肾素的内在依赖性，而是系统对钠缺失的反应性。
