Elevated L-arginine/dimethylarginine ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits

Elevated L-arginine/dimethylarginine ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits
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DOI:
10.1006/bbrc.1996.0279
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发表时间:
1996-02-15
影响因子:
3.1
通讯作者:
Frolich, JC
Frolich, JC
中科院分区:
生物学4区
文献类型:
--
作者:
BodeBoger, SM;Boger, RH;Frolich, JC

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在高胆固醇喂养的家兔中,补充内源性NO的前体L-精氨酸可增强内皮功能。然而,膳食L-精氨酸实现这些作用的机制尚不清楚。在本研究中,我们已经评估了血浆浓度的L-精氨酸和不对称的二甲基精氨酸(ADMA),一个已知的内源性抑制剂NO合成酶,在胆固醇喂养的兔子或没有饮食补充L-精氨酸。尿硝酸盐排泄率作为内源性NO形成的指标进行评估。血浆L-精氨酸水平没有不同的控制和胆固醇喂养的兔子。但在喂食胆固醇+L-精氨酸的兔子中,它们升高了近三倍。血浆ADMA浓度增加约2倍,高胆固醇血症,但不受饮食L-精氨酸。因此,膳食L-精氨酸升高血浆L-精氨酸/ADMA比高于正常水平,并部分恢复尿硝酸盐排泄,这是减少高胆固醇血症。我们的结论是,升高的L-精氨酸/ADMA的比例可能至少部分地解释了恢复NO的形成外源性L-精氨酸在高胆固醇血症。(C)北京:科学出版社. Inc.
Dietary supplementation of L-arginine, the precursor of endogenous NO, has been shown to enhance endothelial function in the cholesterol-fed rabbits. However, the mechanism by which dietary L-arginine accomplishes these effects has been unclear. In the present study we have assessed the plasma concentrations of L-arginine and of asymmetrical dimethylarginine (ADMA), a known endogenous inhibitor of NO synthase, in cholesterol-fed rabbits with or without dietary supplementation of L-arginine. Urinary nitrate excretion rates were assessed as an index of endogenous NO formation. Plasma L-arginine levels were not different between control and cholesterol-fed rabbits. but they were elevated nearly threefold in rabbits fed cholesterol + L-arginine. Plasma ADMA concentration increased about two-fold in hyper-cholesterolemia, but was unaffected by dietary L-arginine. Thus, dietary L-arginine elevated the plasma L-arginine/ADMA ratio above the normal level, and partly restored urinary nitrate excretion, which was decreased by hypercholesterolemia. We conclude that elevation of the L-arginine/ADMA ratio may at least partly explain the restored NO formation by exogenous L-arginine in hypercholesterolemia. (C) 1996 Academic Press. Inc.