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[长期应用L-精氨酸对慢性缺氧大鼠肺动脉平滑肌细胞钾通道的影响]

[The effects of long-term application of L-arginine on K+ channel in pulmonary artery smooth muscle cells from rats exposed to chronic hypoxia].

作者信息

Zhang Yong-chang, Ni Wang, Zhen Guo-hua, Zhang Zhen-xiang, Xu Yong-jian

机构信息

Respiratory Department of Tongji Hospital, Tongji Medical School of Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2003 Feb;26(2):93-6.

Abstract

OBJECTIVE

To investigate the effects of long-term application of L-arginine (L-Arg) on K(+) channel in pulmonary artery smooth muscle cells (PASMC) from rats exposed to chronic hypoxia.

METHODS

Male Wistar rats were randomly divided into three groups: group A (control group), group B (chronic hypoxia group) and group C (chronic hypoxia plus L-Arg treatment group). The rats were exsanguinated and the intrapulmonary arteries (300 approximately 700 OD) were collected. Single PASMC was obtained by the acute enzyme separation method (collagnase Iplus papain) and the conventional whole-cell patch clamp technique was used to record resting membrane potential (Em), potassium ion currents of voltage-gated potassium channel and Ca(2+)-sensitive potassium channel.

RESULTS

(1) The Em of group B [(-31 +/- 8) mV, n = 6] was significantly higher than that of group A [(-42 +/- 5) mV, n = 6, P < 0.01]. After long-term application of L-Arg, the Em of group C [(-39 +/- 4) mV, n = 6] was significantly lower than that of group B (P < 0.05). (2) The peak current at +50 mV of voltage-gated potassium channel was compared among three groups. In group B [(62.2 +/- 5.3) pA/pF, n = 6], it was significantly lower than that of group A [(121 +/- 9) pA/pF, n = 6] (P < 0.01). After long-term application of L-Arg, the peak current at +50 mV of voltage-gated potassium channel in group C [(95 +/- 3) pA/pF, n = 6] was significantly higher than that of group B (P < 0.001). (3) The peak current at +50 mV of Ca(2+)-sensitive potassium channel was compared among three groups. In group B [(74.7 +/- 4.1) pA/pF, n = 6], it was significantly higher than that of group A [(53.6 +/- 5.9) pA/pF, n = 6] (P < 0.05). After long-term application of L-Arg, the peak current at +50 mV of Ca(2+)-sensitive potassium channel in group C [(31.8 +/- 1.8) pA/pF, n = 6] was significantly lower than that of group B [(74.7 +/- 4.1) pA/pF, n = 6] (P < 0.001).

CONCLUSIONS

The long-term application of L-Arg can improve the resting membrane potential of PASMCs from rats exposed to chronic hypoxia, increase the currents of voltage-gated potassium channel and decrease the currents of Ca(2+)-sensitive potassium channel. These effects are considered to be effective in improving chronic hypoxic pulmonary hypertension.

摘要

目的

探讨长期应用L-精氨酸(L-Arg)对慢性缺氧大鼠肺动脉平滑肌细胞(PASMC)钾通道的影响。

方法

将雄性Wistar大鼠随机分为三组:A组(对照组)、B组(慢性缺氧组)和C组(慢性缺氧加L-Arg治疗组)。大鼠处死后收集肺内动脉(外径300~700μm)。采用急性酶分离法(Ⅰ型胶原酶加木瓜蛋白酶)获得单个PASMC,运用传统的全细胞膜片钳技术记录静息膜电位(Em)、电压门控钾通道和钙敏感性钾通道的钾离子电流。

结果

(1)B组的Em[(-31±8)mV,n = 6]显著高于A组[(-42±5)mV,n = 6,P < 0.01]。长期应用L-Arg后,C组的Em[(-39±4)mV,n = 6]显著低于B组(P < 0.05)。(2)比较三组电压门控钾通道在+50 mV时的峰值电流。B组[(62.2±5.3)pA/pF,n = 6]显著低于A组[(121±9)pA/pF,n = 6](P < 0.01)。长期应用L-Arg后,C组电压门控钾通道在+50 mV时的峰值电流[(95±3)pA/pF,n = 6]显著高于B组(P < 0.001)。(3)比较三组钙敏感性钾通道在+50 mV时的峰值电流。B组[(74.7±4.1)pA/pF,n = 6]显著高于A组[(53.6±5.9)pA/pF,n = 6](P < 0.05)。长期应用L-Arg后,C组钙敏感性钾通道在+50 mV时的峰值电流[(31.8±1.8)pA/pF,n = 6]显著低于B组[(74.7±4.1)pA/pF,n = 6](P < 0.001)。

结论

长期应用L-Arg可改善慢性缺氧大鼠PASMC的静息膜电位,增加电压门控钾通道电流,降低钙敏感性钾通道电流。这些作用被认为对改善慢性缺氧性肺动脉高压有效。

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