Patterson K W, Deb B, Kavanagh B P, Pearl R G
Department of Anesthesia, Stanford University Medical Center, Stanford, Calif. 94305-5117, USA.
Pharmacology. 1999 May;58(5):246-51. doi: 10.1159/000028287.
Inhaled nitric oxide (NO), a selective pulmonary vasodilator, increases intracellular cyclic guanosine monophosphate. In contrast, adenosine, another selective pulmonary vasodilator, increases intracellular cyclic adenosine monophosphate. There has been only limited study on effects of inhaled NO combined with other pulmonary vasodilators. The current study examined the hypothesis that inhaled NO would potentiate in vivo pulmonary vasodilator effects of adenosine, but not those of sodium nitroprusside (SNP). Like inhaled NO, SNP acts via cyclic guanosine monophosphate. Rabbits were anesthetized and mechanically ventilated. The NO synthesis inhibitor NG-nitro-L-arginine methyl ester was administered. U46619, a thromboxane A2 mimetic, was infused to produce pulmonary hypertension. Rabbits then received either SNP at doses of 0.5, 1, 2, 4, 8, 16, and 32 microg/kg/min or adenosine at doses of 12.5, 25, 50, 100, 150, and 300 microg/kg/min. Hemodynamic measurements were obtained with or without inhaled NO (40 ppm) at each dose of SNP or adenosine. During U46619-induced pulmonary hypertension, inhaled NO decreased pulmonary artery pressure and pulmonary vascular resistance. Adenosine and SNP produced dose-related decreases in pulmonary artery pressure and pulmonary vascular resistance and increases in cardiac output. Inhaled NO decreased pulmonary artery pressure and pulmonary vascular resistance at all doses of adenosine, but had no significant pulmonary vasodilator effects at doses of SNP >0.5 microg/kg/min. We conclude that inhaled NO does not produce additional pulmonary vasodilation over that achieved at higher doses of SNP, but does produce additional vasodilation when combined with a vasodilator having different mechanisms of action. Since both inhaled NO and adenosine produce selective pulmonary vasodilation, such combination therapy may be effective in patients with pulmonary hypertension.
吸入一氧化氮（NO）是一种选择性肺血管扩张剂，可增加细胞内环磷酸鸟苷。相比之下，另一种选择性肺血管扩张剂腺苷可增加细胞内环磷酸腺苷。关于吸入NO与其他肺血管扩张剂联合使用的效果的研究有限。本研究检验了以下假设：吸入NO会增强腺苷在体内的肺血管扩张作用，但不会增强硝普钠（SNP）的作用。与吸入NO一样，SNP通过环磷酸鸟苷起作用。将兔子麻醉并进行机械通气。给予NO合成抑制剂NG-硝基-L-精氨酸甲酯。输注血栓素A2模拟物U46619以诱导肺动脉高压。然后兔子接受剂量为0.5、1、2、4、8、16和32微克/千克/分钟的SNP或剂量为12.5、25、50、100、150和300微克/千克/分钟的腺苷。在每个SNP或腺苷剂量下，在有或没有吸入NO（40 ppm）的情况下进行血流动力学测量。在U46619诱导的肺动脉高压期间，吸入NO可降低肺动脉压和肺血管阻力。腺苷和SNP可使肺动脉压和肺血管阻力呈剂量相关下降，并使心输出量增加。在所有腺苷剂量下，吸入NO均可降低肺动脉压和肺血管阻力，但在SNP剂量>0.5微克/千克/分钟时无明显肺血管扩张作用。我们得出结论，吸入NO不会在高于SNP高剂量时产生额外的肺血管扩张，但与具有不同作用机制的血管扩张剂联合使用时会产生额外的血管扩张作用。由于吸入NO和腺苷均可产生选择性肺血管扩张，这种联合治疗可能对肺动脉高压患者有效。
