高钾血症状态下猪冠状动脉中一氧化氮和内皮源性超极化因子（EDHF）的释放：尼可地尔的作用

Release of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) in porcine coronary arteries exposed to hyperkalemia: effect of nicorandil.

作者信息

Yang Qin, Zhang Rong-Zhen, Yim Anthony P C, He Guo-Wei

机构信息

Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.

出版信息

Ann Thorac Surg. 2005 Jun;79(6):2065-71. doi: 10.1016/j.athoracsur.2004.11.027.

DOI:10.1016/j.athoracsur.2004.11.027

PMID:15919311

Abstract

BACKGROUND

Although the detrimental effect of hyperkalemia on coronary endothelium has been reported, there is no direct evidence regarding the effect of hyperkalemic exposure on nitric oxide (NO) release from the coronary endothelium. In addition, it is unclear whether nicorandil, a KATP channel opener, used as hyperpolarizing cardioplegia or added in hyperkalemic cardioplegic solution may protect endothelial function during cardiac surgery. The present study was designed to clarify NO release and the function of endothelium-derived hyperpolarizing factor (EDHF) in coronary circulation with respect to the effect of hyperkalemia and nicorandil.

METHODS

Nitric oxide was measured by using a NO-specific electrode, and EDHF-mediated relaxation was investigated in a myograph. Substance P- and calcium ionophore A23187-induced NO release was compared in porcine left circumflex coronary arteries before and after 1-hour exposure to 20 mM potassium (K+) at 37 degrees C. In coronary microarteries (diameter 200 to 450 microm), precontracted with U46619, in the presence of indomethacin (7 microM), NG-nitro-L-arginine (300 microM), and oxyhemoglobin (20 microM), EDHF-mediated relaxation was induced by bradykinin (-10 to -6.5 log M) after incubation with Krebs (control) or 20 mM K+ with or without 10 microM nicorandil at 37 degrees C for 1 hour.

RESULTS

Neither substance P (58.8 +/- 5.0 versus 66.2 +/- 7.2 nmol/L) nor A23187 (86.6 +/- 9.0 versus 82.4 +/- 9.2 nmol/L in control) induced NO release was altered by hyperkalemic exposure (p > 0.05). In contrast, EDHF-mediated relaxation was decreased from 84.2% +/- 3.8% to 42.3% +/- 6.0% (p < 0.001) that was partially restored by nicorandil (50.7% +/- 5.5%, p < 0.05).

CONCLUSIONS

Exposure to potassium at 20 mM does not affect NO release but impairs EDHF-mediated relaxation in coronary arteries. Supplementation of nicorandil in hyperkalemic cardioplegia may provide a protective effect on EDHF-related endothelial function.

摘要

背景

尽管已有报道高钾血症对冠状动脉内皮有不良影响，但关于高钾暴露对冠状动脉内皮一氧化氮（NO）释放的影响尚无直接证据。此外，作为超极化心脏停搏液使用或添加到高钾心脏停搏液中的KATP通道开放剂尼可地尔在心脏手术期间是否能保护内皮功能尚不清楚。本研究旨在阐明高钾血症和尼可地尔对冠状动脉循环中NO释放及内皮衍生超极化因子（EDHF）功能的影响。

方法

使用NO特异性电极测量NO，并在肌动描记器中研究EDHF介导的舒张。比较猪左旋冠状动脉在37℃下暴露于20 mM钾（K+）1小时前后，P物质和钙离子载体A23187诱导的NO释放。在冠状动脉微动脉（直径200至450微米）中，用U46619预收缩，在存在吲哚美辛（7 microM）、NG-硝基-L-精氨酸（300 microM）和氧合血红蛋白（20 microM）的情况下，在37℃下与 Krebs（对照）或20 mM K+孵育1小时，有无10 microM尼可地尔，然后用缓激肽（-10至-6.5 log M）诱导EDHF介导的舒张。

结果

高钾暴露后，P物质（58.8±5.0对66.2±7.2 nmol/L）和A23187（对照中86.6±9.0对82.4±9.2 nmol/L）诱导的NO释放均未改变（p>0.05）。相反，EDHF介导的舒张从84.2%±3.8%降至42.3%±6.0%（p<0.001），尼可地尔可部分恢复（50.7%±5.5%，p<0.05）。