Gozal D, Torres J E, Gozal Y M, Littwin S M
Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
J Appl Physiol (1985). 1996 Nov;81(5):2068-77. doi: 10.1152/jappl.1996.81.5.2068.
Nitric oxide synthase (NOS) blockade was used to test the cardioventilatory responses to hypercapnia and hypoxia in freely behaving animals. Chronically instrumented adult Sprague-Dawley rats were studied before and after intravenous administration of either 100 mg/kg of NG-nitro-L-arginine methyl ester (L-NAME), a nonspecific NOS blocker, or 10 mg/kg of S-methyl-L-thiocitrulline (SMTC), a selective neural NOS inhibitor. L-NAME injection induced sustained blood pressure (BP) elevation with transient tachycardia and increased minute ventilation (VE), which returned to baseline within minutes. SMTC elicited similar, although transient, BP increases; however, heart rate and VE decreased. L-NAME and SMTC did not modify overall steady-state hypercapnic responses. In control conditions, hypoxia induced early VE increases with further VE enhancements at 30 min. L-NAME increased the early VE response to 10% O2 but induced late VE reductions in hypoxia. SMTC did not change early VE responses but induced marked reductions in the later VE hypoxic responses. In control animals, hypoxia induced a significant heart rate increase. This increase was absent during the early response after SMTC and was followed in both L-NAME- and SMTC-treated animals by significant heart rate reductions to values below room air. Similarly, the sustained BP response to hypoxia in control animals was absent after administration of NOS inhibitors. These findings suggest that NOS activity exerts excitatory influences on respiration and cardiac chronotropy and sustained vasomotor tone during hypoxia. We speculate that NOS-mediated mechanisms may play an important role in hypoxia-induced ventilatory roll-off during wakefulness.
一氧化氮合酶（NOS）阻断被用于测试自由活动动物对高碳酸血症和低氧血症的心肺通气反应。对成年Sprague-Dawley大鼠进行长期仪器植入，在静脉注射100 mg/kg的NG-硝基-L-精氨酸甲酯（L-NAME，一种非特异性NOS阻断剂）或10 mg/kg的S-甲基-L-硫代瓜氨酸（SMTC，一种选择性神经NOS抑制剂）之前和之后进行研究。注射L-NAME会导致血压（BP）持续升高，伴有短暂心动过速，分钟通气量（VE）增加，数分钟内恢复至基线水平。SMTC引起类似但短暂的血压升高；然而，心率和VE下降。L-NAME和SMTC并未改变整体稳态高碳酸血症反应。在对照条件下，低氧血症会在早期引起VE增加，并在30分钟时进一步增强VE。L-NAME增加了对10% O₂的早期VE反应，但在低氧血症时导致后期VE降低。SMTC并未改变早期VE反应，但导致后期低氧血症VE反应显著降低。在对照动物中，低氧血症会导致显著的心率增加。在注射SMTC后的早期反应中未出现这种增加，并且在L-NAME和SMTC处理的动物中，随后心率显著降低至低于室内空气的值。同样，在给予NOS抑制剂后，对照动物中对低氧血症的持续血压反应消失。这些发现表明，NOS活性在低氧血症期间对呼吸、心脏变时性和持续血管运动张力发挥兴奋作用。我们推测，NOS介导的机制可能在清醒期间低氧血症诱导的通气衰减中起重要作用。
