Nitric oxide and effects of cationic polypeptides in canine cerebral arteries.
Nitric oxide and effects of cationic polypeptides in canine cerebral arteries.
复制标题
一氧化氮和阳离子多肽在犬脑动脉中的作用。
DOI：
10.1097/00004647-199704000-00013
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Katusic,ZS
中科院分区：
文献类型：
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作者：
Kinoshita,H;Katusic,ZS
阳离子多肽由活化的白细胞释放，并可能在调节血管张力中起重要作用。尚未研究阳离子多肽对脑血管张力的影响。本实验旨在确定合成的阳离子多肽，聚-L-精氨酸和聚-L-赖氨酸，是否影响脑动脉功能。将有内皮和无内皮的犬基底动脉环悬挂，用于等长力记录。聚-L-精氨酸（10-8-10- 7 M）和聚-L-赖氨酸（10-8-10- 7 M）引起内皮依赖性舒张。一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯（10- 4 M）和一氧化氮清除剂氧合血红蛋白（3 × 10- 6 M）可抑制阳离子多肽引起的舒张反应。带负电荷的分子，肝素（1 U/ml）和硫酸葡聚糖（10 mg/ml），也抑制松弛聚-L-精氨酸或聚-L-赖氨酸。高浓度的聚-L-精氨酸（10 ~（-6）~ 10 ~（-5）M）和聚-L-赖氨酸（10 ~（-6）~ 10 ~（-5）M）可引起非内皮依赖性收缩。蛋白激酶C抑制剂，staurosporine（10- 8 M），取消这些收缩。肝素（10 U/ml）和硫酸葡聚糖（100 mg/ml）抑制阳离子多肽的收缩作用，但不影响对佛波醇12，13-二丁酸酯的收缩。聚-L-精氨酸（10- 6 M）和聚-L-赖氨酸（10- 6 M）可阻断缓激肽（10-10-10- 6 M）或钙离子载体A23187（10-9-10- 6 M）引起的内皮依赖性舒张反应。肝素（50 U/ml）和硫酸葡聚糖（200 mg/ml）可恢复暴露于聚-L-精氨酸（10- 6 M）或聚-L-赖氨酸（10 - 6 M）的动脉中缓激肽（10-10-10- 6 M）的内皮依赖性舒张。这些研究表明，在较低浓度范围（10-8-10- 7 M）内，聚-L-精氨酸和聚-L-赖氨酸通过电荷依赖性激活内皮一氧化氮合酶产生一氧化氮，诱导内皮依赖性舒张。在较高的浓度范围（10-6-10- 5 M），阳离子多肽引起内皮非依赖性收缩以及内皮依赖性舒张功能受损，以响应缓激肽和A23187。这些收缩和内皮依赖性舒张的抑制也由电荷依赖性机制介导，并可能涉及蛋白激酶C的激活。
Cationic polypeptides are released by activated leukocytes and may play an important role in the regulation of vascular tone. Effects of cationic polypeptides on cerebral vascular tone have not been studied. The present experiments were designed to determine if synthetic cationic polypeptides, poly-L-arginine and poly-L-lysine, affect the function of cerebral arteries. Rings of canine basilar arteries with and without endothelium were suspended for isometric force recording. Poly-L-arginine (10–8–10–7M) and poly-L-lysine (10–8–10–7M) caused endothelium-dependent relaxations. A nitric oxide synthase inhibitor,NG-nitro-L-arginine methyl ester (10–4M), and a nitric oxide scavenger, oxyhemoglobin (3 × 10–6M), inhibited relaxations in response to cationic polypeptides. Negatively charged molecules, heparin (1 U/ml) and dextran sulfate (10 mg/ml), also inhibited relaxations to poly-L-arginine or poly-L-lysine. Higher concentrations of poly-L-arginine (10–6–10–5M) and poly-L-lysine (10–6–10–5M) induced endothelium-independent contractions. A protein kinase C inhibitor, staurosporine (10–8M), abolished these contractions. Heparin (10 U/ml) and dextran sulfate (100 mg/ml) inhibited the contractile effect of cationic polypeptides but did not affect contractions to phorbol 12,13-dibutyrate. Poly-L-arginine (10–6M) and poly-L-lysine (10–6M) abolished endothelium-dependent relaxations in response to bradykinin (10–10–10–6M) or calcium ionophore A23187 (10–9–10–6M). Heparin (50 U/ml) and dextran sulfate (200 mg/ml) restored endothelium-dependent relaxations to bradykinin (10–10–10–6M) in arteries exposed to poly-L-arginine (10–6M) or poly-L-lysine (10–6M). These studies demonstrate that in the lower concentration range (10–8–10–7M), poly-L-arginine and poly-L-lysine induce endothelium-dependent relaxations by production of nitric oxide via charge-dependent activation of endothelial nitric oxide synthase. In the higher concentration range (10–6–10–5M), cationic polypeptides cause endothelium-independent contractions as well as impairment of endothelium-dependent relaxations in response to bradykinin and A23187. These contractions and inhibition of endothelium-dependent relaxations are also mediated by a charge-dependent mechanism and may involve activation of protein kinase C.