Haemodynamic and biochemical responses to L-arginine and L-lysine infusions in normal subjects: L-arginine-induced vasodilatation cannot be explained by non-specific effects of cationic amino acids.
Haemodynamic and biochemical responses to L-arginine and L-lysine infusions in normal subjects: L-arginine-induced vasodilatation cannot be explained by non-specific effects of cationic amino acids.
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DOI：
10.1042/cs0920367
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发表时间：
1997-04
期刊：
影响因子：
6
通讯作者：
R. Smulders;M. Aarsen;T. Teerlink;P. Vries;G. Kamp;A. Donker;C. Stehouwer
中科院分区：
文献类型：
--
作者：
R. Smulders;M. Aarsen;T. Teerlink;P. Vries;G. Kamp;A. Donker;C. Stehouwer
1.药理学刺激一氧化氮（NO）的合成在预防或治疗心血管疾病中可能是重要的。2.关于NO的前体L-精氨酸是否能够刺激基础内皮NO的产生有很多讨论。已知L-精氨酸具有血管舒张作用。然而，目前尚不清楚L-精氨酸诱导的血管舒张是否可归因于NO产生的增加或L-精氨酸的其他全身作用。3.为了进一步研究L-精氨酸诱导的血管舒张的机制，我们比较了健康受试者对L-精氨酸与生理盐水和L-赖氨酸的反应。L-赖氨酸不是NO合成的底物，但具有L-精氨酸的许多其他性质。4.在L-精氨酸输注期间，血压降低[收缩压从120.2（SD 8.8）降至117.3（12.1）mmHg（P = 0.05）;舒张压从65.3（5.9）降至61.6（7.9）mmHg（P < 0.01）]，心率和细胞外液量增加。L-精氨酸输注后外周血管总阻力降低18.0（11.4）%（与基线和L-赖氨酸输注相比P <或= 0.05）。这些结果表明血管舒张。L-赖氨酸和生理盐水输注期间未观察到变化。5.血浆cGMP（NO第二信使）在L-精氨酸和L-赖氨酸输注期间均升高[分别从5.7（1.2）~ 6.8（1.7）nmol/l（P < 0.01）和5.8（1.8）~ 7.0（2.9）nmol/l（P < 0.05）]。L-精氨酸输注期间血浆L-瓜氨酸（L-精氨酸合成NO的副产物）从30.6（7.5）增加到47.1（9.9）mumol/l（P < 0.001），L-赖氨酸输注期间也从32.7（6.5）增加到42.0（8.3）mumol/l（P < 0.001）。6.血浆电解质和心房利钠肽浓度对L-精氨酸和L-赖氨酸输注的反应相似，表明对渗透压、血浆容量扩张和钾分布的影响相似。7.总之，虽然L-赖氨酸输注的效果与L-精氨酸输注相似，但未观察到血管舒张。因此，这些作用不能解释L-精氨酸诱导的血管舒张。这一发现间接支持了这一假设，即在L-精氨酸输注过程中的血管舒张可能是由NO合成的增加介导的。如果是这样，我们的数据表明，NO合成的假定标志物，血浆环GMP和L-瓜氨酸浓度，不能准确反映这种增加。相反，血浆cGMP的升高可能与ANP的升高有关。L-瓜氨酸的升高可能与L-精氨酸竞争相同的细胞膜转运机制和刺激尿素循环有关。
1. Pharmacological stimulation of the synthesis of nitric oxide (NO) may be important in the prevention or treatment of cardiovascular diseases. 2. There is much discussion as to whether the precursor of NO, L-arginine, is able to stimulate basal endothelial NO production. L-Arginine is known to have vasodilating effects. However, it is not clear whether L-arginine-induced vasodilatation is attributable to an increase in NO production or to other systemic effects of L-arginine. 3. To investigate further the mechanisms of the L-arginine-induced vasodilatation, we compared the responses to L-arginine with those to saline and L-lysine in healthy subjects. L-Lysine is not a substrate for NO synthesis, but shares many of L-arginine's other properties. 4. During L-arginine infusion, blood pressure decreased [systolic blood pressure from 120.2 (SD 8.8) to 117.3 (12.1) mmHg (P = 0.05); diastolic blood pressure from 65.3 (5.9) to 61.6 (7.9) mmHg (P < 0.01)], and heart rate and extracellular fluid volume increased. The total peripheral vascular resistance decreased during L-arginine infusion by 18.0 (11.4)% (P < or = 0.05 compared with baseline and compared with L-lysine infusion). These results indicate vasodilation. No changes were observed during L-lysine and saline infusion. 5. Plasma cyclic GMP (the second messenger for NO) increased during L-arginine but also during L-lysine infusion [from 5.7 (1.2) to 6.8 (1.7) nmol/l (P < 0.01), and from 5.8 (1.8) to 7.0 (2.9) nmol/l (P < 0.05) respectively]. Plasma L-citrulline (a by-product of NO synthesis from L-arginine) increased during L-arginine infusion from 30.6 (7.5) to 47.1 (9.9) mumol/l (P < 0.001), but also during L-lysine infusion from 32.7 (6.5) to 42.0 (8.3) mumol/l (P < 0.001). 6. Plasma electrolytes and atrial natriuretic peptide concentrations responded similarly to L-arginine and L-lysine infusion, indicating similar effects on osmolality, plasma volume expansion and potassium distribution. 7. In conclusion, although L-lysine infusion had effects that were similar to those of L-arginine infusion, no vasodilatation was observed. Therefore, these effects cannot account for the L-arginine-induced vasodilatation. This finding indirectly supports the hypothesis that the vasodilatation during L-arginine infusion might be mediated by an increase in NO synthesis. If so, our data suggest that the presumed markers for NO synthesis, plasma cyclic GMP and L-citrulline concentrations, do not accurately reflect this increase. Instead, the rise in plasma cyclic GMP may be related to the rise in ANP. The rise in L-citrulline may be related to competition with L-arginine for the same cell membrane transport mechanism and to stimulation of the urea cycle.