The renal and systemic hemodynamic effects of a nitric oxide-synthase inhibitor are reversed by a selective endothelinA receptor antagonist in men
The renal and systemic hemodynamic effects of a nitric oxide-synthase inhibitor are reversed by a selective endothelinA receptor antagonist in men
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DOI：
10.1006/niox.2001.0357
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发表时间：
2001-08-01
影响因子：
3.9
通讯作者：
Schmetterer, L
中科院分区：
文献类型：
--
作者：
Schmidt, A;Bayerle-Eder, M;Schmetterer, L
有证据表明，一氧化氮（NO）和内皮素（ET）之间的相互作用，在肾血管系统的水平。我们假设，在健康人中，全身性NO合酶抑制剂（N-G-单甲基-L-精氨酸，L-NMMA）的急性肾脏效应可能会被特定ETA受体拮抗剂（BQ-123）联合给药所减弱。15名健康年轻男性受试者参加了这项随机、双盲、安慰剂对照的3向交叉研究。这些钠补充的志愿者单独接受L-NMMA，或单独接受BQ-123，或L-NMMA与随后的BQ-123共输注。分别用PAH和菊粉清除法测定肾血浆流量（RPF）和肾小球滤过率（GFR）。平均动脉压（MAP）和脉率在基线和研究期开始后每15分钟进行一次无创测量。单独使用L-NMMA可降低RPF（-22%，P < 0.001）和GFR（-8%，P < 0.009），增加MAP（+10%，P < 0.001）。单独使用BQ-123不会影响这些参数。但BQ-123联合给药可减弱L-NMMA对RPF（P < 0.001）、GFR（P < 0.001）和MAP（P = 0.006）的影响。急性全身性NO合酶抑制的外周和肾脏血液动力学效应至少部分被BQ-123的ETA受体阻断剂逆转。这表明特异性ETA受体拮抗剂和NO合酶抑制剂之间在肾血管系统水平的功能性拮抗作用。(C)北京：科学出版社.
There is evidence for an interaction between nitric oxide (NO) and endothelin (ET) at the level of the renal vasculature. We hypothesized that acute renal effects of systemic NO synthase inhibition (N-G-monomethyl-L-arginine, L-NMMA) may be blunted by coadministration of a specific ETA receptor antagonist (BQ-123) in healthy humans. Fifteen healthy young male subjects participated in this randomized, double-blind, placebo-controlled 3-way crossover study. These sodium-repleted volunteers received L-NMMA alone, or BQ-123 alone, or L-NMMA with a subsequent coinfusion of BQ-123. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were determined with the PAH and inulin clearance method, respectively. Mean arterial pressure (MAP) and pulse rate were measured noninvasively at baseline and every 15 min after the start of the study period. L-NMMA, alone reduced RPF (-22%, P < 0.001) and GFR (-8%, P < 0.009) and increased MAP (+10%, P < 0.001). BQ-123 alone did not affect these parameters. However, coinfusion of BQ-123 blunted the effects of L-NMMA on RPF (P < 0.001), GFR (P < 0.001), and MAP (P = 0.006). Peripheral and renal hemodynamic effects of acute systemic NO synthase inhibition are at least partially reversed by ETA receptor blockade with BQ-123. This indicates a functional antagonism between specific ETA receptor antagonist and NO synthase inhibitors at the level of the renal vasculature. (C) 2001 Academic Press.