Holden W E, Kishiyama S S, Dong S P, Osborne M L
Department of Medicine, Portland VA Medical Center, Oregon.
Toxicol Appl Pharmacol. 1990 Jun 15;104(2):191-9. doi: 10.1016/0041-008x(90)90294-5.
The acute effects of cigarette smoking on the pulmonary vasculature are poorly understood--both vasodilatory and vasoconstrictive effects have been described. To investigate the mechanisms involved, strips of pig intrapulmonary arteries with and without intact endothelium were exposed to an extract of cigarette smoke made by bubbling smoke through phosphate-buffered saline. After contraction with norepinephrine (2.5 X 10(-7) M), smoke extract (concentration range 0.001 to 0.5%) caused a biphasic response in strips with intact endothelium--relaxation at lower concentrations and contraction at higher concentrations. Both relaxation and contraction responses were absent in strips without endothelium. Blockade of muscarinic, beta adrenergic, serotonergic, and histamine type 1 and 2 receptors did not alter the effects. Indomethacin (5 X 10(-6) M) or acetylsalicylic acid (10(-4) M) blocked the relaxation but not contraction effects of smoke extract, suggesting that relaxation was due to cyclooxygenase products of arachidonic acid. Nicotine caused endothelium-dependent contraction of intrapulmonary arteries and the contractile effects of both nicotine and smoke extract were blocked by hexamethonium (10(-6) M). However, the contractile effects of cigarette smoke components are more potent than those of nicotine. These findings help explain previously described acute effects of smoking on the pulmonary vasculature and provide insight into the mechanisms involved.
吸烟对肺血管系统的急性影响目前了解甚少——既有血管舒张作用，也有血管收缩作用的相关描述。为了研究其中涉及的机制，将有完整内皮和无完整内皮的猪肺内动脉条暴露于通过磷酸盐缓冲盐水鼓泡烟雾制成的香烟烟雾提取物中。在用去甲肾上腺素（2.5×10⁻⁷M）收缩后，烟雾提取物（浓度范围0.001%至0.5%）在有完整内皮的动脉条中引起双相反应——较低浓度时舒张，较高浓度时收缩。无内皮的动脉条中既无舒张反应也无收缩反应。阻断毒蕈碱、β肾上腺素能、5-羟色胺能以及组胺1型和2型受体并不改变这些效应。吲哚美辛（5×10⁻⁶M）或乙酰水杨酸（10⁻⁴M）阻断了烟雾提取物的舒张作用，但未阻断其收缩作用，这表明舒张是由于花生四烯酸的环氧化酶产物所致。尼古丁引起肺内动脉的内皮依赖性收缩，六甲铵（10⁻⁶M）可阻断尼古丁和烟雾提取物的收缩作用。然而，香烟烟雾成分的收缩作用比尼古丁更强。这些发现有助于解释先前描述的吸烟对肺血管系统的急性影响，并为其中涉及的机制提供了见解。
