Dubuis Eric, Potier Marie, Wang Rui, Vandier Christophe
LABPART, Faculté de Médecine, 2 bis Boulevard Tonnellé, 37032 Tours, France.
Cardiovasc Res. 2005 Feb 15;65(3):751-61. doi: 10.1016/j.cardiores.2004.11.007.
We tested the hypothesis that inhalation of a low concentration of exogenous carbon monoxide (CO) attenuates the development of hypoxic pulmonary artery hypertension by activation of large-conductance voltage and Ca(2+)-activated K(+) channels (BK(Ca)).
The BK(Ca) activity was measured using whole-cell and inside-out patch clamp recordings in Wistar rat pulmonary artery (PA) myocytes. Pulmonary artery pressures were measured in vivo and membrane potentials were recorded in vitro in pressurized resistance arteries.
Chronic CO inhalation slightly increases single-channel conductance of BK(Ca) channels and induces a large increase in the sensitivity of BK(Ca) channels to Ca(2+) of PA myocytes from normoxic and chronic hypoxic rats. Consequently, BK(Ca) currents are increased and play a more prominent role in controlling resting membrane potential of PA myocytes. Chronic CO inhalation also reduces hemodynamic changes induced by chronic hypoxia and attenuates hypoxic pulmonary artery hypertension.
Chronic inhalation of CO attenuates hypoxic pulmonary artery hypertension development presumably through activation of BK(Ca) channels. These results highlight the potential use of CO as a novel avenue for research on the treatment of pulmonary artery hypertension (PAHT) in a similar manner to another gasotransmitter, nitric oxide.
我们检验了如下假设，即吸入低浓度外源性一氧化碳（CO）通过激活大电导电压和钙激活钾通道（BK（Ca））来减轻缺氧性肺动脉高压的发展。
使用全细胞膜片钳和内面向外膜片钳记录技术在Wistar大鼠肺动脉（PA）肌细胞中测量BK（Ca）活性。在体内测量肺动脉压力，在体外加压阻力动脉中记录膜电位。
慢性吸入CO可轻微增加BK（Ca）通道的单通道电导，并使常氧和慢性缺氧大鼠PA肌细胞的BK（Ca）通道对Ca2+的敏感性大幅增加。因此，BK（Ca）电流增加，并在控制PA肌细胞静息膜电位中发挥更突出的作用。慢性吸入CO还可减少慢性缺氧引起的血流动力学变化，并减轻缺氧性肺动脉高压。
慢性吸入CO可能通过激活BK（Ca）通道来减轻缺氧性肺动脉高压的发展。这些结果突出了CO作为一种新型途径用于研究肺动脉高压（PAHT）治疗的潜力，其方式类似于另一种气体信号分子一氧化氮。
