L-瓜氨酸对兔血管平滑肌的舒张作用。

Relaxant effects of L-citrulline in rabbit vascular smooth muscle.

作者信息

Ruiz E, Tejerina T

机构信息

Department of Pharmacology, School of Medicine, Complutense University, Madrid, Spain.

出版信息

Br J Pharmacol. 1998 Sep;125(1):186-92. doi: 10.1038/sj.bjp.0702051.

DOI:10.1038/sj.bjp.0702051

PMID:9776359

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565602/

Abstract

Vascular endothelium plays a pivotal role in the control of vascular tone through the release of vasoactive factors such as EDRF (NO). 2. The aim of this study was to investigate whether the addition of exogenous L-citrulline, the byproduct of the NO-synthesis, could relax vascular smooth muscle. 3. L-citrulline relaxed both endothelium-denuded and endothelium-intact rabbit aortic rings precontracted with noradrenaline 10(-6) M (maximum relaxations induced by L-citrulline 10(-8) M were 74.1+/-5.2% vs 51.3+/-2.8% in endothelium-denuded and endothelium-intact arteries, respectively). 4. This relaxant effect was enhanced by zaprinast (a phosphodiesterase type 5 inhibitor) and inhibited by HS-142-1 (a particulate guanylate cyclase inhibitor) and by apamin (a K(Ca)-channel blocker). 5. L-citrulline (10(-13)-10(-8) M) increased cGMP levels in aortic rings (maximum value with L-citrulline 10(-8) M was 0.165+/-0.010 pmol cGMP mg(-1) of tissue vs 0.038+/-0.009 pmol mg(-1) of tissue in basal). 6. L-citrulline as well as NO were released from endothelial cells in culture stimulated with ACh. The values were 6.50+/-0.50 microM vs 2.30+/-0.20 microM (stimulated with ACh and basal respectively) for L-citrulline and 4.22+/-0.10 microM vs 0.87+/-0.26 microM (stimulated with ACh and basal respectively) for NO. 7. These results suggest that L-citrulline could be released together with NO from endothelium and may have actions complementary to those of NO in the control of vascular smooth muscle relaxation.

摘要

血管内皮通过释放如内皮舒张因子（一氧化氮）等血管活性因子，在控制血管张力方面发挥关键作用。2. 本研究的目的是探究添加外源性L-瓜氨酸（一氧化氮合成的副产物）是否能舒张血管平滑肌。3. L-瓜氨酸使预先用10⁻⁶M去甲肾上腺素预收缩的去内皮和完整内皮兔主动脉环舒张（L-瓜氨酸10⁻⁸M诱导的最大舒张率在去内皮动脉中为74.1±5.2%，在完整内皮动脉中为51.3±2.8%）。4. 这种舒张作用被扎普司特（一种5型磷酸二酯酶抑制剂）增强，被HS-142-1（一种颗粒型鸟苷酸环化酶抑制剂）和蜂毒明肽（一种钙激活钾通道阻滞剂）抑制。5. L-瓜氨酸（10⁻¹³ - 10⁻⁸M）增加主动脉环中的环鸟苷酸水平（L-瓜氨酸10⁻⁸M时的最大值为0.165±0.010 pmol环鸟苷酸/毫克组织，而基础值为0.038±0.009 pmol/毫克组织）。6. 用乙酰胆碱刺激培养的内皮细胞时，L-瓜氨酸以及一氧化氮从内皮细胞释放。L-瓜氨酸的值分别为6.50±0.50微摩尔/升（用乙酰胆碱刺激）和2.30±0.20微摩尔/升（基础值），一氧化氮的值分别为4.22±0.10微摩尔/升（用乙酰胆碱刺激）和0.87±0.26微摩尔/升（基础值）。7. 这些结果表明，L-瓜氨酸可能与一氧化氮一起从内皮释放，并且在控制血管平滑肌舒张方面可能具有与一氧化氮互补的作用。