Schneider J C, Blazy I, Déchaux M, Rabier D, Mason N P, Richalet J P
Association pour la Recherche en Physiologie de l'Environnement, UFR Médecine, Bobigny, France.
Eur Respir J. 2001 Aug;18(2):286-92. doi: 10.1183/09031936.01.00073401.
It was hypothesized that hypoxia may inhibit nitric oxide (NO) production by reducing the availability of endothelial NO synthase (NOS III) substrate. To evaluate the effect of L-arginine on the NO release in high altitude, 11 subjects were infused with L-arginine (0.5 g x kg(-1)) during 30 min in normoxia and after 36 h at 4,350 m (hypoxia). The L-citrulline and cyclic guanosine monophosphate (cGMP) concentrations were measured to investigate NO synthesis and guanylyl cyclase activity respectively. L-citrulline concentration, arterial oxygen saturation (Sa,O2), systemic blood pressure, heart rate and acute mountain sickness (AMS) score were measured at rest and 15, 30 and 45 min after starting infusion. The results showed that baseline L-citrulline was lower in hypoxia (p<0.05). L-arginine infusion increased L-citrulline concentration in both conditions. However, in hypoxia L-citrulline concentration remained lower than in normoxia (p<0.05). The concentration of cGMP was lower in hypoxia (p<0.05). In hypoxia, Sa,O2 increased from 15 min after the start of the infusion to 45 min (p<0.05). Blood pressure and heart rate were not affected by L-arginine infusion. Subjects who experienced symptoms of AMS showed a slight decrease in AMS score with L-arginine. The decreased L-citrulline suggests a hypoxia-induced impairment of nitric oxide synthase III or a decrease in L-arginine availability. The improvement of arterial oxygen saturation by pretreatment with L-arginine could be ascribed to an enhancement of the ventilation/perfusion ratio. Collectively, these results are consistent with a decrease in nitric oxide production in hypoxia that could be antagonized by supplying nitric oxide synthase cosubstrate.
研究假设，缺氧可能通过降低内皮型一氧化氮合酶（NOS III）底物的可用性来抑制一氧化氮（NO）的产生。为了评估L-精氨酸对高海拔地区NO释放的影响，11名受试者在常氧条件下30分钟内以及在海拔4350米处（缺氧）36小时后静脉输注L-精氨酸（0.5 g·kg⁻¹）。分别测量L-瓜氨酸和环磷酸鸟苷（cGMP）浓度，以研究NO合成和鸟苷酸环化酶活性。在静息状态以及开始输注后15、30和45分钟测量L-瓜氨酸浓度、动脉血氧饱和度（SaO₂）、全身血压、心率和急性高山病（AMS）评分。结果显示，缺氧时基线L-瓜氨酸水平较低（p<0.05）。在两种条件下，输注L-精氨酸均使L-瓜氨酸浓度升高。然而，缺氧时L-瓜氨酸浓度仍低于常氧状态（p<0.05）。缺氧时cGMP浓度较低（p<0.05）。在缺氧状态下，从输注开始后15分钟至45分钟，SaO₂升高（p<0.05）。血压和心率不受L-精氨酸输注的影响。出现AMS症状的受试者，L-精氨酸治疗后AMS评分略有下降。L-瓜氨酸减少提示缺氧诱导一氧化氮合酶III功能受损或L-精氨酸可用性降低。L-精氨酸预处理可改善动脉血氧饱和度，这可能归因于通气/灌注比的提高。总体而言，这些结果与缺氧时一氧化氮产生减少一致，补充一氧化氮合酶辅助底物可对抗这种减少。
