Liu Rong, Evgenov Oleg V, Ichinose Fumito
Dept. of Anesthesia and Critical Care, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA.
J Appl Physiol (1985). 2005 Feb;98(2):748-52. doi: 10.1152/japplphysiol.00820.2004. Epub 2004 Oct 1.
Nitric oxide (NO), synthesized by NO synthases (NOS), plays a pivotal role in regulation of pulmonary vascular tone. To examine the role of endothelial NOS (NOS3) in hypoxic pulmonary vasoconstriction (HPV), we measured left lung pulmonary vascular resistance (LPVR), intrapulmonary shunting, and arterial PO2 (PaO2) before and during left mainstem bronchus occlusion (LMBO) in mice with and without a deletion of the gene encoding NOS3. The increase of LPVR induced by LMBO was greater in NOS3-deficient mice than in wild-type mice (151 +/- 39% vs. 109 +/- 36%, mean +/- SD; P < 0.05). NOS3-deficient mice had a lower intrapulmonary shunt fraction than wild-type mice (17.1 +/- 3.6% vs. 21.7 +/- 2.4%, P < 0.05) during LMBO. Both real-time PaO2 monitoring with an intra-arterial probe and arterial blood-gas analysis during LMBO showed higher PaO2 in NOS3-deficient mice than in wild-type mice (P < 0.05). Inhibition of all three NOS isoforms with Nomega-nitro-L-arginine methyl ester (L-NAME) augmented the increase of LPVR induced by LMBO in wild-type mice (183 +/- 67% in L-NAME treated vs. 109 +/- 36% in saline treated, P < 0.01) but not in NOS3-deficient mice. Similarly, systemic oxygenation during one-lung ventilation was augmented by L-NAME in wild-type mice but not in NOS3-deficient mice. These findings indicate that NO derived from NOS3 modulates HPV in vivo and that inhibition of NOS3 improves systemic oxygenation during acute unilateral lung hypoxia.
由一氧化氮合酶（NOS）合成的一氧化氮（NO）在肺血管张力调节中起关键作用。为了研究内皮型一氧化氮合酶（NOS3）在低氧性肺血管收缩（HPV）中的作用，我们在左主支气管闭塞（LMBO）之前和期间，测量了野生型和基因编码NOS3缺失的小鼠的左肺肺血管阻力（LPVR）、肺内分流和动脉血氧分压（PaO2）。与野生型小鼠相比，NOS3基因缺失小鼠中由LMBO诱导的LPVR增加幅度更大（分别为151±39%和109±36%，平均值±标准差；P<0.05）。在LMBO期间，NOS3基因缺失小鼠的肺内分流分数低于野生型小鼠（分别为17.1±3.6%和21.7±2.4%，P<0.05）。在LMBO期间，通过动脉内探头进行的实时PaO2监测以及动脉血气分析均显示，NOS3基因缺失小鼠的PaO2高于野生型小鼠（P<0.05）。用Nω-硝基-L-精氨酸甲酯（L-NAME）抑制所有三种NOS同工型，可增强野生型小鼠中由LMBO诱导的LPVR增加（L-NAME处理组为183±67% vs. 生理盐水处理组为109±36%，P<0.01），但对NOS3基因缺失小鼠无此作用。同样，在单肺通气期间，L-NAME可改善野生型小鼠的全身氧合，但对NOS3基因缺失小鼠无此作用。这些结果表明，源自NOS3的NO在体内调节HPV作用，并且抑制NOS3可改善急性单侧肺缺氧期间的全身氧合。
