Uncles D R, Daugherty M O, Frank D U, Roos C M, Rich G F
Department of Anesthesiology, University of Virginia, Charlottesville, USA.
Anesth Analg. 1996 Dec;83(6):1212-7. doi: 10.1097/00000539-199612000-00014.
Nitric oxide (NO) or endothelium-derived relaxing factor may play an important role in modulating pulmonary vascular resistance (PVR), although previous studies have produced conflicting results. Endogenous NO inhibition causes an increase in PVR in intact animals but not in saline-perfused isolated lungs. We hypothesized that blood is essential for NO to serve as a modulator of PVR. Therefore, the effects of endogenous NO inhibition (N omega-nitro-L-arginine methyl ester [L-NAME]) were determined in isolated rat lungs as related to the presence of different blood components under normoxic conditions and after 1 wk of hypoxia (fraction of inspired oxygen [FIO2] = 10%). Exogenously administered inhaled NO was evaluated in isolated lungs from normoxic and hypoxic rats. In normoxic rats, L-NAME (10-100 microM) caused a dose-dependent increase in PVR in whole (hematocrit [Hct] 40%) and diluted (Hct 12%) blood-perfused lungs. L-NAME (10-800 microM) had no effect in isolated lungs perfused with a modified salt solution of equal viscosity to blood either alone, or containing plasma (50%) or free oxyhemoglobin (10 microM). In whole blood perfused lungs, L-NAME (100 microM) increased PVR more in hypoxic versus normoxic isolated lungs (141% vs 100%). Inhaled NO decreased PVR in isolated lungs from hypoxic rats and partially reversed the effects of L-NAME, but had no effect in normoxic lungs. In conclusion, endogenous and inhaled NO modulate PVR in isolated rat lungs and this role is increased by prolonged hypoxia. The response to inhibition of endogenous NO is dependent on the presence of red blood cells and is independent of the changes in viscosity or the presence of oxyhemoglobin or plasma.
一氧化氮（NO）或内皮源性舒张因子可能在调节肺血管阻力（PVR）中发挥重要作用，尽管先前的研究结果相互矛盾。内源性NO抑制可使完整动物的PVR升高，但在生理盐水灌注的离体肺中则不然。我们推测血液对于NO作为PVR的调节因子至关重要。因此，在常氧条件下以及缺氧1周后（吸入氧分数[FIO2]=10%），研究了内源性NO抑制（Nω-硝基-L-精氨酸甲酯[L-NAME]）对离体大鼠肺的影响，这些影响与不同血液成分的存在有关。对常氧和缺氧大鼠的离体肺进行了外源性吸入NO的评估。在常氧大鼠中，L-NAME（10-100μM）可使全血（血细胞比容[Hct]40%）和稀释血（Hct 12%）灌注的肺中的PVR呈剂量依赖性升高。L-NAME（10-800μM）对单独灌注等粘度血液改良盐溶液、含血浆（50%）或游离氧合血红蛋白（10μM）的离体肺均无影响。在全血灌注的肺中，L-NAME（100μM）在缺氧离体肺中比在常氧离体肺中使PVR升高得更多（分别为141%和100%）。吸入NO可降低缺氧大鼠离体肺中的PVR，并部分逆转L-NAME的作用，但对常氧肺无影响。总之，内源性和吸入性NO可调节离体大鼠肺中的PVR，长期缺氧会增强这种作用。对内源性NO抑制的反应取决于红细胞的存在，且与粘度变化、氧合血红蛋白或血浆的存在无关。
