Konduri G G, Mital S
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Biol Neonate. 2000 Oct;78(3):220-9. doi: 10.1159/000014274.
We investigated the hypothesis that the purine nucleotide ATP and its nucleoside adenosine cause pulmonary vasodilation in fetal lambs by the release of nitric oxide (NO). We also investigated the potential role of K(+)(ATP) channels in mediating the effects of ATP and adenosine on NO. We surgically prepared 28 fetal lambs to measure pulmonary and systemic pressures and pulmonary flow. We investigated the effects of glibenclamide and pinacidil (inhibitor and agonist, respectively, for K(+)(ATP) channels), N-nitro-L-arginine (N-LA) and its methyl ester, N-nitro-L-arginine methyl ester (L-NAME) (inhibitors of endothelium-derived NO synthesis), and U46619 (a thromboxane mimetic) on pulmonary vasodilation caused by adenosine and ATP. Adenosine decreased the pulmonary artery pressure and pulmonary vascular resistance (PVR) at doses of 0.08-2.5 microM/kg/min and increased the left pulmonary flow at doses of 0.3-2.5 microM/kg/min in control experiments. N-LA, L-NAME and glibenclamide attenuated the effects of adenosine at doses of < 2.5 microM/ kg/min and pinacidil potentiated its effects. ATP decreased the pulmonary artery pressure and PVR and increased the pulmonary flow at doses of 0.15-2.5 microM/kg/min in control experiments. N-LA and L-NAME attenuated the effects of ATP at doses of < 2.5 microM/kg/min, whereas glibenclamide and pinacidil had no effect on the response to ATP. U46619 increased the basal pulmonary vascular tone, but did not significantly alter the vasodilative responses to ATP and adenosine. In conclusion, adenosine and ATP cause NO-dependent pulmonary vasodilation in fetal lambs. The activation of K(+)(ATP) channels plays a role in adenosine-induced pulmonary vasodilation. The mechanism by which ATP causes NO release and pulmonary vasodilation requires further investigation.
嘌呤核苷酸三磷酸腺苷（ATP）及其核苷腺苷通过释放一氧化氮（NO）引起胎羊肺血管舒张。我们还研究了ATP敏感性钾（K(+)(ATP)）通道在介导ATP和腺苷对NO的作用中的潜在作用。我们通过手术准备了28只胎羊，以测量肺和全身压力以及肺血流量。我们研究了格列本脲和吡那地尔（分别为K(+)(ATP)通道的抑制剂和激动剂）、N-硝基-L-精氨酸（N-LA）及其甲酯N-硝基-L-精氨酸甲酯（L-NAME）（内皮源性NO合成的抑制剂）以及U46619（一种血栓素类似物）对腺苷和ATP引起的肺血管舒张的影响。在对照实验中，腺苷以0.08 - 2.5微摩尔/千克/分钟的剂量降低肺动脉压力和肺血管阻力（PVR），并以0.3 - 2.5微摩尔/千克/分钟的剂量增加左肺血流量。N-LA、L-NAME和格列本脲在剂量<2.5微摩尔/千克/分钟时减弱了腺苷的作用，而吡那地尔增强了其作用。在对照实验中，ATP以0.15 - 2.5微摩尔/千克/分钟的剂量降低肺动脉压力和PVR并增加肺血流量。N-LA和L-NAME在剂量<2.5微摩尔/千克/分钟时减弱了ATP的作用，而格列本脲和吡那地尔对ATP的反应没有影响。U46619增加了基础肺血管张力，但没有显著改变对ATP和腺苷的血管舒张反应。总之，腺苷和ATP在胎羊中引起依赖NO的肺血管舒张。K(+)(ATP)通道的激活在腺苷诱导的肺血管舒张中起作用。ATP引起NO释放和肺血管舒张的机制需要进一步研究。
