Cederqvist B, Persson M G, Gustafsson L E
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Biochem Pharmacol. 1994 Mar 15;47(6):1047-53. doi: 10.1016/0006-2952(94)90416-2.
Previous studies, utilizing nitric oxide synthase inhibitors and nitric oxide application, indicate that nitric oxide has the capacity to modulate contractile responses in pulmonary vessels. In the present study, in vitro effects of organic nitrates/nitrites were compared with their in vivo ability to generate nitric oxide and their effects on blood pressure. Glyceryl trinitrate, ethyl nitrite, isobutyl nitrate, isobutyl nitrite, isoamyl nitrite and butyl nitrite inhibited contractions in response to nerve stimulation in guinea pig pulmonary artery and vas deferens. Glyceryl trinitrate (also known as nitroglycerin) was the most potent and isobutyl nitrate the least potent substance with this action (IC50 4.5 +/- 0.2 x 10(-10) and 1.1 +/- 0.1 x 10(-5) M, respectively). Contractile responses to noradrenaline were inhibited, whereas noradrenaline release was unaffected by organonitrates/nitrites, indicating a post-junctional inhibitory effect. When infused intravenously to anaesthetized rabbits glyceryl trinitrate, ethyl nitrite and isobutyl nitrate generated dose-dependent increments of nitric oxide in exhaled air and dose-dependent decrements in systemic blood pressure. Significant correlations were obtained between in vivo NO generation and effects on blood pressure, as well as between NO generation in vivo and the in vitro activity of the organic nitrites and organic nitrates. In conclusion, organic nitrites and organic nitrates can modulate adrenergic neuroeffector transmission in guinea pig pulmonary artery and vas deferens, and produce detectable concentrations of nitric oxide in exhaled air in vivo, in the rabbit. The observations give direct in vivo evidence that organic nitrites and nitrates generate NO, and strongly support them exerting their action via NO formation.
以往利用一氧化氮合酶抑制剂和应用一氧化氮的研究表明，一氧化氮有调节肺血管收缩反应的能力。在本研究中，将有机硝酸盐/亚硝酸盐的体外效应与其体内生成一氧化氮的能力及其对血压的影响进行了比较。硝酸甘油、亚硝酸乙酯、硝酸异丁酯、亚硝酸异丁酯、亚硝酸异戊酯和亚硝酸丁酯抑制豚鼠肺动脉和输精管对神经刺激的收缩反应。硝酸甘油（也称为硝化甘油）在此作用中效力最强，硝酸异丁酯效力最弱（IC50分别为4.5±0.2×10⁻¹⁰和1.1±0.1×10⁻⁵M）。对去甲肾上腺素的收缩反应受到抑制，而去甲肾上腺素的释放不受有机硝酸盐/亚硝酸盐的影响，表明是一种节后抑制作用。当静脉注射到麻醉兔体内时，硝酸甘油、亚硝酸乙酯和硝酸异丁酯使呼出空气中的一氧化氮呈剂量依赖性增加，使全身血压呈剂量依赖性降低。体内一氧化氮生成与对血压的影响之间，以及体内一氧化氮生成与有机亚硝酸盐和有机硝酸盐的体外活性之间均获得了显著相关性。总之，有机亚硝酸盐和有机硝酸盐可调节豚鼠肺动脉和输精管中的肾上腺素能神经效应传递，并在兔体内呼出空气中产生可检测浓度的一氧化氮。这些观察结果提供了体内直接证据，证明有机亚硝酸盐和硝酸盐可生成一氧化氮，并有力地支持它们通过一氧化氮的形成发挥作用。
