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心房利钠肽对大鼠急性容量负荷应激时血流动力学和肾脏反应的放大作用。

Amplification by atrial natriuretic peptide of the haemodynamic and renal responses to an acute volumic stress in the rat.

作者信息

Caron N, Simon F, Plennevaux F, Michel A, Kramp R

机构信息

Service de Physiologie et Pharmacologie, Université de Mons-Hainaut, Mons, Belgium.

出版信息

Clin Exp Pharmacol Physiol. 1999 Apr;26(4):315-22. doi: 10.1046/j.1440-1681.1999.03035.x.

DOI:10.1046/j.1440-1681.1999.03035.x
PMID:10225142
Abstract
  1. The purpose of the present study was to test the effects of synthetic atrial natriuretic peptide (ANP) on renal haemodynamics and excretory capacities of salt and water in the rat during an 'acute volumic stress', which was induced by brisk disturbances of the circulatory volume. 2. To this end, 29 anaesthetized male Wistar rats were rapidly injected with 1 mL of 0.85% NaCl, repeated twice at 60 s intervals. The injectates contained no ANP (n = 5) or 1 x 0.25 (n = 6), 3 x 0.25 (n = 6), 1 x 2.5 (n = 6) or 3 x 2.5 micrograms (n = 6) ANP, added to the first injectate only (1 x) or to each injectate (3 x). Renal blood flow (RBF) was continuously measured with an electromagnetic flow transducer. 3. Renal blood flow increased transiently (approximately 30 s) by approximately 13% (P < 0.05) during each injection of saline without ANP. Addition of 0.25 or 2.5 micrograms ANP to the first injectate enhanced RBF by 21 and 35%, respectively (both P < 0.05), but did not modify the time sequence. Furthermore, addition of 0.25 microgram ANP to the second and third injectate produced an almost similar change in RBF at the end of each injection (delta RBF = 20 and 17%, respectively). In contrast, the addition of 2.5 micrograms ANP to the second and third injectate did not produce the same changes in RBF observed at the end of the first injection. The amplitude of the change in RBF was then similar to the increase in RBF induced by 1 mL saline without ANP. Mean arterial pressure (MAP) did not change significantly during repeated injections of saline alone or with addition of 0.25 microgram ANP to the first injectate. However, MAP decreased significantly (by 5, 9 and 9 mmHg) after the injection of 3 x 0.25, 1 x 2.5 or 3 x 2.5 micrograms ANP, respectively. 4. Sodium excretion was rapidly increased from 2.600 +/- 0.654 to 9.330 +/- 1.322 mumol/min after injection of 3 x 1 mL of 0.85% NaCl (P < 0.05). Thereafter, sodium excretion remained enhanced throughout the experiment, so that 70% of the sodium load injected was recovered at the end of the experiment. Atrial natriuretic peptide added to the injectates further elevated the maximal responses in diuresis and natriuresis induced by saline injections without ANP (P < 0.001). A maximal effect was observed after the addition of 2.5 micrograms ANP to the first saline solution. When the amount of sodium excreted was calculated by integrating the areas under the curve of the natriuretic responses, a relationship was established as a function of the amount of ANP added to the saline solutions. It was characterized by a threshold in the presence of 2.5 micrograms ANP added to the first injectate when the integration period was limited to 4 min 30 s and 14 min 30 s after starting the first injection of the varying test solutions. When the integration period was extended until the end of the experiment (2 h), the amount of sodium excreted in each group was further enhanced, especially after injection of 3 x 1 mL of 0.85% NaCl without ANP or with 1 x 0.25 and 3 x 0.25 microgram ANP. Differences in sodium excretion between groups were attenuated (P < 0.054, ANOVA). 5. In conclusion, our results demonstrate differential effects of synthetic ANP on renal vascular reactivity and excretory capacity. These effects were superimposed on changes induced by acute volumic stress. In particular, effects of saline injections on renal vascular compliance were amplified in the presence of ANP added in varying amounts to the injectates. This amplification was limited to 2.5 micrograms ANP.
摘要
  1. 本研究的目的是测试合成心房利钠肽(ANP)在“急性容量应激”期间对大鼠肾血流动力学以及盐和水排泄能力的影响,该“急性容量应激”由循环容量的快速扰动诱发。2. 为此,对29只麻醉的雄性Wistar大鼠快速注射1 mL 0.85%氯化钠溶液,每隔60秒重复注射一次,共注射两次。注射液中不含ANP(n = 5)或添加了1×0.25(n = 6)、3×0.25(n = 6)、1×2.5(n = 6)或3×2.5微克(n = 6)ANP,仅添加到第一次注射液中(1×)或添加到每次注射液中(3×)。用电磁流量传感器连续测量肾血流量(RBF)。3. 在每次注射不含ANP的生理盐水期间,肾血流量短暂增加(约30秒)约13%(P < 0.05)。在第一次注射液中添加0.25或2.5微克ANP分别使RBF增加21%和35%(均P < 0.05),但未改变时间顺序。此外,在第二次和第三次注射液中添加0.25微克ANP在每次注射结束时使RBF产生几乎相似的变化(ΔRBF分别为20%和17%)。相反,在第二次和第三次注射液中添加2.5微克ANP在第一次注射结束时未产生相同的RBF变化。RBF变化的幅度随后与注射1 mL不含ANP的生理盐水引起的RBF增加相似。在单独重复注射生理盐水或在第一次注射液中添加0.25微克ANP期间,平均动脉压(MAP)无显著变化。然而,分别注射3×0.25、1×2.5或3×2.5微克ANP后,MAP显著降低(分别降低5、9和9 mmHg)。4. 注射3×1 mL 0.85%氯化钠溶液后,钠排泄量从2.600±0.654迅速增加到9.330±1.322微摩尔/分钟(P < 0.05)。此后,在整个实验过程中钠排泄量持续增加,以至于在实验结束时回收了70%注入的钠负荷。添加到注射液中的心房利钠肽进一步提高了由不含ANP的生理盐水注射诱导的利尿和利钠的最大反应(P < 0.001)。在第一次生理盐水溶液中添加2.5微克ANP后观察到最大效应。当通过对利钠反应曲线下面积进行积分来计算钠排泄量时,建立了与添加到生理盐水溶液中的ANP量相关的关系。其特征是当积分期限制在开始注射不同测试溶液后的4分30秒和14分30秒时,在第一次注射液中添加2.5微克ANP存在阈值。当积分期延长至实验结束(2小时)时,每组的钠排泄量进一步增加,特别是在注射3×1 mL不含ANP的0.85%氯化钠溶液或添加1×0.25和3×0.25微克ANP的溶液后。各组之间钠排泄的差异减小(P < 0.054,方差分析)。5. 总之,我们的结果证明了合成ANP对肾血管反应性和排泄能力的不同影响。这些影响叠加在急性容量应激引起的变化之上。特别是,在向注射液中添加不同量ANP的情况下,生理盐水注射对肾血管顺应性的影响得到放大。这种放大仅限于2.5微克ANP。

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