Pinheiro J M, Malik A B
Department of Pediatrics, Albany Medical College of Union University, New York 12208.
Am J Physiol. 1992 Nov;263(5 Pt 2):H1532-6. doi: 10.1152/ajpheart.1992.263.5.H1532.
We studied the potential role of ATP-sensitive potassium (K+ATP) channel activation in mediating pulmonary vasodilation in newborn piglets. Piglet lungs (n = 14, ages 1-4 days) were artificially perfused with recirculating Ringer solution containing bovine serum albumin and statistically inflated using 95% O2-5% CO2. We measured pulmonary arterial pressure (Ppa) and distribution of pulmonary vascular resistance (using double-occlusion method). Under resting conditions (Ppa 13.7 +/- 1.6 cmH2O, mean +/- SE), the K+ATP channel agonist BRL 38227 (lemakalim, 10(-7) and 10(-6) M) caused small dose-dependent pulmonary vasodilation. This response was diminished by the K+ATP-channel blocker glibenclamide (10(-5) M). Pretreatment of lungs with indomethacin (10(-5) M) and N omega-nitro-L-arginine (10(-5) M) to inhibit cyclooxygenase- and nitric oxide (NO)-related vasodilation, respectively, resulted in a marked increase in the baseline Ppa to 85.6 +/- 11.2 cmH2O. Injection of BRL 38227 (10(-7) M and 10(-6) M) in these lungs decreased Ppa to 72.5 +/- 8.5 (P < 0.01) and 19.3 +/- 0.9 cmH2O (P < 0.01), respectively; the corresponding times for half-recovery of Ppa (t1/2R) were 5.7 +/- 4.3 and > 20 min. Glibenclamide (10(-5) M) abolished the response to 10(-7) M BRL 38227 and significantly diminished (P < 0.05) the decreases in Ppa and t1/2R in response to 10(-6) M BRL 38227 but not to acetylcholine (10(-10) M). We conclude that activation of K+ATP channels has a minimal role in maintaining basal pulmonary vasomotor tone but is able to induce marked vasodilation when NO and cyclooxygenase-dependent vasodilatory mechanisms are inhibited.
我们研究了ATP敏感性钾通道（K+ATP通道）激活在介导新生仔猪肺血管舒张中的潜在作用。用含牛血清白蛋白的循环林格氏液对仔猪肺（n = 14，年龄1 - 4天）进行人工灌注，并使用95% O2 - 5% CO2进行统计学充气。我们测量了肺动脉压（Ppa）和肺血管阻力分布（采用双阻断法）。在静息状态下（Ppa 13.7 ± 1.6 cmH2O，平均值 ± 标准误），K+ATP通道激动剂BRL 38227（雷马卡林，10^(-7)和10^(-6) M）引起小剂量依赖性肺血管舒张。这种反应被K+ATP通道阻滞剂格列本脲（10^(-5) M）减弱。分别用吲哚美辛（10^(-5) M）和Nω-硝基-L-精氨酸（10^(-5) M）预处理肺以抑制环氧化酶相关和一氧化氮（NO）相关的血管舒张，导致基线Ppa显著升高至85.6 ± 11.2 cmH2O。在这些肺中注射BRL 38227（10^(-7) M和10^(-6) M）分别使Ppa降至72.5 ± 8.5（P < 0.01）和19.3 ± 0.9 cmH2O（P < 0.01）；Ppa恢复一半的相应时间（t1/2R）分别为5.7 ± 4.3和> 20分钟。格列本脲（10^(-5) M）消除了对10^(-7) M BRL 38227的反应，并显著减弱（P < 0.05）了对10^(-6) M BRL 38227的Ppa降低和t1/2R，但对乙酰胆碱（10^(-10) M）没有影响。我们得出结论，K+ATP通道的激活在维持基础肺血管舒缩张力方面作用最小，但当NO和环氧化酶依赖性血管舒张机制被抑制时能够诱导显著的血管舒张。
