肺动脉高压患者单次服用伐地那非后血浆不对称二甲基精氨酸、对称二甲基精氨酸和精氨酸水平的变化。
Changes in plasma levels of asymmetric dimethylarginine, symmetric dimethylarginine, and arginine after a single dose of vardenafil in patients with pulmonary hypertension.
作者信息
Henrohn Dan, Sandqvist Anna, Egeröd Hanna, Hedeland Mikael, Wernroth Lisa, Bondesson Ulf, Wikström Gerhard
机构信息
Department of Medical Sciences, Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå University Hospital, Umeå, Sweden.
出版信息
Vascul Pharmacol. 2015 Oct;73:71-7. doi: 10.1016/j.vph.2015.04.010. Epub 2015 Apr 29.
OBJECTIVE
We investigated whether vardenafil, a phosphodiesterase-5 inhibitor, alters plasma levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and arginine.
PATIENTS AND METHODS
ADMA, SDMA, and arginine were measured (0-540 min) in 12 patients with pulmonary hypertension after a single oral dose of vardenafil. Invasive hemodynamic data were collected at baseline and after 60 min.
RESULTS
A reduction in ADMA was observed at 30 and 45 min with a median change of -11.1% (P=0.021) and -12.5% (P=0.002). SDMA decreased with a median -5.3% change (P=0.032) at 45 min. An increase in arginine, median 40.3% (P=0.002), 45.0% (P=0.010), and 77.1% (P=0.008) was observed at 120, 300, and 540 min respectively. An increase in the arginine/ADMA ratio, median 11.7% (P=0.012), 32.5% (P=0.003), 26.5% (P=0.021), 33% (P=0.007), 48.5% (P=0.007), and 63.1% (P=0.008) was observed at 15, 45, 60, 120, 300, and 540 min respectively. There was a positive correlation between vardenafil exposure and the percent change in the arginine/ADMA ratio from baseline to 540 min (r=0.80; P=0.01). A correlation between baseline mean right atrial pressure (mRAP) and baseline ADMA (r=0.65; P=0.023), and baseline SDMA (r=0.61; P=0.035) was observed. A correlation between the baseline arginine/ADMA ratio and baseline cardiac output (CO) (r=0.59; P=0.045) and baseline cardiac index (CI) (r=0.61; P=0.036) was observed. Baseline arginine/ADMA ratio correlated with baseline mRAP (r=-0.79; P=0.002). A correlation between change (0-60 min) in CI and change in arginine (r=0.77; P=0.003) as well as change in the arginine/ADMA ratio (r=0.61; P=0.037) was observed.
CONCLUSIONS
Vardenafil induced changes in ADMA, SDMA, arginine, and the arginine/ADMA ratio in patients with PH. An increase in arginine and the arginine/ADMA ratio was associated with improvement in CI.
目的
我们研究了磷酸二酯酶-5抑制剂伐地那非是否会改变不对称二甲基精氨酸（ADMA）、对称二甲基精氨酸（SDMA）和精氨酸的血浆水平。
患者与方法
对12例肺动脉高压患者单次口服伐地那非后（0 - 540分钟）测定ADMA、SDMA和精氨酸水平。在基线和60分钟后收集有创血流动力学数据。
结果
在30分钟和45分钟时观察到ADMA降低，中位数变化分别为-11.1%（P = 0.021）和-12.5%（P = 0.002）。在45分钟时SDMA降低，中位数变化为-5.3%（P = 0.032）。在120分钟、300分钟和540分钟时分别观察到精氨酸增加，中位数分别为40.3%（P = 0.002）、45.0%（P = 0.010）和77.1%（P = 0.008）。在15分钟、45分钟、60分钟、120分钟、300分钟和540分钟时分别观察到精氨酸/ADMA比值增加，中位数分别为11.7%（P = 0.012）、32.5%（P = 0.003）、26.5%（P = 0.021）、33%（P = 0.007）、48.5%（P = 0.007）和63.1%（P = 0.008）。伐地那非暴露量与从基线到540分钟精氨酸/ADMA比值的变化百分比之间存在正相关（r = 0.80；P = 0.01）。观察到基线平均右心房压（mRAP）与基线ADMA（r = 0.65；P = 0.023）以及基线SDMA（r = 0.61；P = 0.035）之间存在相关性。观察到基线精氨酸/ADMA比值与基线心输出量（CO）（r = 0.59；P = 0.045）和基线心脏指数（CI）（r = 0.61；P = 0.036）之间存在相关性。基线精氨酸/ADMA比值与基线mRAP相关（r = -0.79；P = 0.002）。观察到CI的变化（0 - 60分钟）与精氨酸的变化（r = 0.77；P = 0.003）以及精氨酸/ADMA比值的变化（r = 0.61；P = 0.037）之间存在相关性。
结论
伐地那非可引起肺动脉高压患者ADMA、SDMA、精氨酸及精氨酸/ADMA比值的变化。精氨酸和精氨酸/ADMA比值的增加与CI的改善相关。
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