Anderson G H, Streeten D H, Dalakos T G
Circ Res. 1977 Mar;40(3):243-50. doi: 10.1161/01.res.40.3.243.
An angiotensin II (A II) analogue (1-Sar-8-Ala-angiotensin II) (saralasin) was infused into 418 untreated hypertensive subjects during a 1-day evaluation while blood pressure was recorded every 2 minutes by Arteriosonade. At 5 mug/kg per min, saralasin produced a change in mean blood pressure which correlated significantly (r=-0.54, P less than 0.001) with the stimulated plasma renin activity (PRA) (after intravenous furosemide and ambulation for 2 hours. Saralasin caused a rise inmean blood pressure of at least 7.0 mm Hg in 97 hypertensive subjects, who also had a low stimulated PRA (1.3+/-SEM, 0.1 ng/ml per hour; normal range, 1.7-8.5). On a low sodium diet, the pressor response of hypertensive subjects to saralasin continued and was an even better indicator of a low stimulated PRA. Infusion of saralasin at 10 mug/kg per min into normal subjects on an unrestricted diet, a low sodium diet, and a high sodium diet produced, respectively, no change, a fall (P less than 0.05), and a rise (P less than 0.005) in blood pressure. The same saralasin dose in six hypertensive subjects who showed a pressor response to the analogue in the 1-day study also produced a rise in blood pressure when given on a low sodium diet, and this rise was more than twice that seen in normal subjects on a high sodium diet. Hypertensive subjects who showed the pressor response had a significantly greater (P less than 0.01) pressor sensitivity to A II than did hypertensive nonresponders to saralasin and noraml subjects on an uncontrolled diet. The affinity of the vascular receptors for the analogue was greater in the hypertensive group that showed the pressor response to saralasin. In summary, the pressor response to saralasin, as defined above, occurred in 23% of a large unselected group of hypertensive subjects and was associated with salt loading, a low stimulated PRA, and increased pressor sensitivity to A II.
在为期1天的评估期间，将一种血管紧张素II（A II）类似物（1-肌氨酸-8-丙氨酸血管紧张素II）（沙拉新）输注到418名未经治疗的高血压受试者体内，同时通过动脉声纳每2分钟记录一次血压。以每分钟5微克/千克的速度输注沙拉新时，其引起的平均血压变化与刺激后的血浆肾素活性（PRA）显著相关（r = -0.54，P < 0.001）（静脉注射速尿并活动2小时后）。沙拉新使97名高血压受试者的平均血压升高至少7.0毫米汞柱，这些受试者的刺激后PRA也较低（1.3±标准误，每小时0.1纳克/毫升；正常范围为1.7 - 8.5）。在低钠饮食情况下，高血压受试者对沙拉新的升压反应持续存在，并且是低刺激PRA的更好指标。以每分钟10微克/千克的速度将沙拉新输注到饮食不受限制、低钠饮食和高钠饮食的正常受试者体内，分别导致血压无变化、下降（P < 0.05）和升高（P < 0.005）。在1天研究中对该类似物有升压反应的6名高血压受试者，在低钠饮食时给予相同剂量的沙拉新也会导致血压升高，且这种升高幅度是高钠饮食的正常受试者的两倍多。出现升压反应的高血压受试者对A II的升压敏感性显著高于对沙拉新无反应的高血压受试者以及饮食未受控制的正常受试者（P < 0.01）。在对沙拉新有升压反应的高血压组中，血管受体对该类似物的亲和力更大。总之，上述定义的对沙拉新的升压反应发生在一大组未经挑选的高血压受试者中的23%，并且与盐负荷、低刺激PRA以及对A II的升压敏感性增加有关。
