Human renal and systemic hemodynamic, natriuretic, and neurohumoral responses to different doses of L-NAME
Human renal and systemic hemodynamic, natriuretic, and neurohumoral responses to different doses of L-NAME
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DOI：
10.1152/ajprenal.1998.275.6.f870
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发表时间：
1998-12-01
影响因子：
4.2
通讯作者：
Schalekamp, MADH
中科院分区：
文献类型：
--
作者：
Broere, A;Van den MEiracker, AH;Schalekamp, MADH
实验证据表明，肾循环比其他血管床对一氧化氮（NO）合成抑制的影响更敏感。为了探索在男性中，NO介导的血管舒张张力在肾中是否大于在体循环中，三种不同的静脉内输注N（G）-硝基-L-精氨酸甲酯（L-NAME; 1、5和25 μ g.kg（-1）.min（-1），30 min）或安慰剂对平均动脉压（MAP）、体循环血管阻力（SVR）、肾血流量（RBF）、在12名健康受试者中研究了肾血管阻力（RVR）、肾小球滤过率（GFR）和钠和锂排泄分数（FE（Na）和FE（Li）），每个受试者在两种不同的情况下随机接受四种治疗中的两种。通过Finapres装置连续测量MAP，并通过模型流量法计算每搏输出量。根据放射性标记的邻苯二甲酸盐和马尿酸清除率估计GFR和RBF。输注开始后，对全身和肾脏血流动力学进行2小时随访。在安慰剂期间，肾脏和全身血流动力学以及FEN和FELi保持稳定。在低和中等L-NAME剂量下，SVR和RVR的最大增量相似：低剂量分别为20.4 +/- 19.6和23.5 +/-16.0%，中等剂量分别为31.4 +/- 26.7和31.2 +/-14.4%（平均值+/- SD）。随着L-NAME剂量的增加，RVR的增加大于SVR的增加。尽管RBF、FEN和FELi降低，但在低剂量L-NAME下没有变化，但在中等剂量下分别降低了31.2 +/- 11.0和20.2 +/-6.3%，在高剂量下分别降低了70.8 +/- 8.1和31.5 +/- 15.9%。它的结论是，在男性的肾循环是不是更敏感的NO合成抑制的影响比体循环和NO合成抑制产生抗白尿的阈值高于阈值水平，导致肾血管收缩。
Experimental evidence indicates that the renal circulation is more sensitive to the effects of nitric oxide (NO) synthesis inhibition than other vascular beds. To explore whether in men the NO-mediated vasodilator tone is greater in the renal than in the systemic circulation, the effects of three different intravenous infusions of N(G)-nitro-L-arginine methyl ester (L-NAME; 1, 5, and 25 mu g.kg(-1).min(-1) for 30 min) or placebo on mean arterial pressure (MAP), systemic vascular resistance (SVR), renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), and fractional sodium and lithium excretion (FE(Na) and FE(Li)) were studied in 12 healthy subjects, each receiving randomly two of the four treatments on two different occasions. MAP was measured continuously by means of the Finapres device, and stroke volume was calculated by a model flow method. GFR and RBF were estimated from the clearances of radiolabeled thalamate and hippuran. Systemic and renal hemodynamics were followed for 2 h after start of infusions. During placebo, renal and systemic hemodynamics and FEN, and FELi remained stable. With the low and intermediate L-NAME doses, maximal increments in SVR and RVR were similar: 20.4 +/- 19.6 and 23.5 +/- 16.0%, respectively, with the low dose and 31.4 +/- 26.7 and 31.2 +/- 14.4%, respectively, with the intermediate dose (means +/- SD). With the high L-NAME dose, the increment in RVR was greater than the increment in SVR. Despite a decrease in RBF, FEN, and FELi did not change with the low L-NAME dose, but they decreased by 31.2 +/- 11.0 and 20.2 +/- 6.3%, respectively, with the intermediate dose and by 70.8 +/- 8.1 and 31.5 +/- 15.9% with the high L-NAME dose, respectively. It is concluded that in men the renal circulation is not more sensitive to the effects of NO synthesis inhibition than the systemic circulation and that the threshold for NO synthesis inhibition to produce antinatriuresis is higher than the threshold level to cause renal vasoconstriction.