慢性低氧对大鼠肺血管L-精氨酸/一氧化氮途径的影响

Effect of chronic hypoxia on L-Arginine/nitric oxide pathway in rat pulmonary artery

目的 :探讨慢性低氧对大鼠肺血管L -精氨酸 /一氧化氮 (L -Arg/NO)途径的影响。方法 :采用慢性低氧性肺动脉高压 (HPH)大鼠肺血管孵育 ,测定慢性HPH对大鼠肺动脉L -Arg转运 ,一氧化氮合酶 (NOS)活性和NO生成释放的影响。结果 :(1)低氧 4周大鼠肺动脉平均压 (mPAP)比对照组高 33 7% (P <0 0 1) ,右心室 (RV)和左室加室间隔 (LV +S)重量比值 (RV/LV +S)高 44 2 % (P <0 0 1)。 (2 )低氧对血浆L -Arg含量无明显影响。 (3)低氧大鼠离体孵育的肺动脉摄取低浓度 (0 2mmol/L)和高浓度 (5 0mmol/L) [3H]-L -Arg分别低于对照组 15 8% (P <0 0 5 )和 2 7 2 % (P <0 0 1)。 (4)低氧大鼠肺动脉tNOS、iNOS和cNOS活性较对照组高 38 0 %、32 8%和 5 3 0 % (P <0 0 1)。 (5 )低氧大鼠血浆NO含量低于对照组 ,与mPAP和RV/LV +S呈负相关 (P <0 0 1)。结论 :慢性HPH时NOS活性代偿性增强 ,但L -Arg转运受损使血浆NO生成仍减少 ,说明L

AIM: To study the effect of chronic hypoxia on L-Arginine/NO pathway in rat pulmonary artery. METHODS: Changes in pulmonary artery L-Arginine(L-Arg) transport, nitric oxide synthase (NOS) activity, plasma nitrite level and L-Arg level in HPH rats were investigated. RESULTS: (1) The mean pulmonary arterial pressure (mPAP) and weight ratio of right ventricle to left ventricle and septum (RV/LV+S) of HPH group were higher than those in control group (P<0.01). (2) Plasma L-Arg level in HPH group was not significantly changed. (3) At low (0.2 mmol/L)or high(5.0 mmol/L)concentration of L-Arg, the velocity of L-Arg transport in HPH group was lower than that in control group (P<0.05 or P<0.01). (4) The activity of pulmonary artery tNOS, iNOS and cNOS in HPH group were increased by 38.0%, 32.8% and 53.0%, respectively (P<0.01), compared with control group. (5) Plasma NO level of HPH group was decreased, which was negative correlation to mPAP and RV/LV+S (P<0、01). CONCLUSION: The decrease of nitric oxide generation might result from L-Arg transport injury, while pulmonary artery tNOS, iNOS and cNOS activity were enhanced during chronic hypoxia.