L-ARGININE AUGMENTS ENDOTHELIUM-DEPENDENT VASODILATION IN CHOLESTEROL-FED RABBITS
L-ARGININE AUGMENTS ENDOTHELIUM-DEPENDENT VASODILATION IN CHOLESTEROL-FED RABBITS
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DOI：
10.1161/01.res.67.6.1301
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发表时间：
1990-12-01
影响因子：
20.1
通讯作者：
CREAGER, MA
中科院分区：
文献类型：
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作者：
GIRERD, XJ;HIRSCH, AT;CREAGER, MA
有证据表明，内皮源性舒张因子是一氧化氮，L-精氨酸是体外合成一氧化氮的前体。外源性L-精氨酸是否参与了体内血管平滑肌张力的调节仍存在争议。在高胆固醇血症，阻力血管不放松正常的药理学刺激释放内皮衍生的舒张因子;生物测定实验表明，受损的合成或释放内皮衍生的舒张因子帐户，在某种程度上，这种迟钝的放松。我们假设高胆固醇血症降低精氨酸代谢，从而损害内皮源性舒张因子合成。因此，我们设计了一项研究，以确定外源性L-精氨酸是否可以增加麻醉胆固醇喂养兔后肢阻力血管内皮依赖性血管舒张。用电磁流量探头记录16只胆固醇喂养兔和12只对照兔的股动脉血流量。在静脉内施用L-精氨酸（10 mg/kg/min）、D-精氨酸（10 mg/kg/min）或盐水之前和期间，研究后肢血管舒张剂对乙酰胆碱（0.3 - 9.0 μ g/kg/min）和硝普钠（0.3 - 9.0 μ g/kg/min）的递增动脉内输注的反应。与对照组相比，胆固醇喂养的家兔对乙酰胆碱的血管舒张反应受损。L-精氨酸增强血管舒张乙酰胆碱在胆固醇喂养，但不是在对照兔。L-精氨酸并没有改变硝普钠在两组中的作用。生理盐水和D-精氨酸都没有改变对乙酰胆碱或硝普钠的反应。我们的数据表明，外源性L-精氨酸可使胆固醇喂养兔后肢阻力血管的内皮依赖性血管舒张正常化。
Evidence exists that an endothelium-derived relaxing factor is nitric oxide and that L-arginine is the precursor for the synthesis of nitric oxide in vitro. Whether exogenous L-arginine contributes to the modulation of vascular smooth muscle tone in vivo is still controversial. In hypercholesterolemia, resistance vessels do not relax normally in response to pharmacological stimuli that release endothelium-derived relaxing factor; bioassay experiments have suggested that impaired synthesis or release of endothelium-derived relaxing factor accounts, in part, of this blunted relaxation. We hypothesized that hypercholesterolemia reduces arginine metabolism and thereby impairs endothelium-derived relaxing factor syntehsis. Accordingly, we designed a study to determine whether exogenous L-arginine could augment endothelium-dependent vasodilation of hind limb resistance vessels in anaesthetized cholesterol-fed rabbits. Femoral blood flow was recorded with an electromagnetic flow probe in 16 cholesterol-fed and 12 control rabbits. The hind limb vasodilator responses to incremental intra-arterial infusions of acethylcholine (0.3-9.0 .mu.g/kg/min) and nitroprusside (0.3-9.0 .mu.g/kg/min) were studied before and during intravenous administration of L-arginine (10 mg/kg/min), D-arginine (10 mg/kg/min), or saline. The vasodilator response to acetylcholine was impaired in cholesterol-fed rabbits as compared with control rabbits. L-Arginine augmented vasodilation to acetylcholine in cholesterol-fed but not in control rabbits. L-Arginine did not alter the effect of nitroprusside in either group. Neither saline nor D-arginine changed the response to either acetylcholine or nitroprusside. Our data demonstrate that exogenous L-arginine normalizes the endothelium-dependent vasodilation of hind limb resistance vessels in cholesterol-fed rabbits.