Carvalho P, Johnson S R, Charan N B
Pulmonary Research Laboratory, Department of Veterans Affairs Medical Center, Boise, Idaho 83702, USA.
J Appl Physiol (1985). 1998 Jan;84(1):215-21. doi: 10.1152/jappl.1998.84.1.215.
We studied the dose-dependent effects of inhaled isoetharine HCl, a beta-adrenergic bronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow (Qbr) in anesthetized sheep. Isoetharine resulted in a dose-dependent increase in Qbr. With a total dose of 17.5 mg, Qbr increased from baseline values of 22 +/- 3.4 (SE) to 60 +/- 16 ml/min (P < 0.001), an effect independent of changes in cardiac output and systemic arterial pressure. To further study whether synthesis of endogenous nitric oxide (NO) affects beta-agonist-induced increases in Qbr, we administered isoetharine (20 mg) by inhalation before and after the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Intravenous L-NAME (30 mg/kg) rapidly decreased Qbr by approximately 80% of baseline, whereas L-NAME via inhalation (10 mg/kg) resulted in a delayed and smaller (approximately 22%) decrease. Pretreatment with L-NAME via both routes of administration attenuated bronchial arterial vasodilation after subsequent challenge with isoetharine. We conclude that isoetharine via inhalation increases Qbr in a dose-dependent manner and that beta-agonist-induced relaxation of vascular smooth muscle in the bronchial vasculature is partially mediated via synthesis of NO.
我们研究了吸入盐酸异他林（一种β - 肾上腺素能支气管扩张剂，剂量分别为2.5、5.0、10.0和20.0毫克）对麻醉绵羊支气管血流量（Qbr）的剂量依赖性影响。异他林使Qbr呈剂量依赖性增加。总剂量为17.5毫克时，Qbr从基线值22±3.4（标准误）增加到60±16毫升/分钟（P<0.001），该效应与心输出量和体动脉压的变化无关。为进一步研究内源性一氧化氮（NO）的合成是否影响β - 激动剂诱导的Qbr增加，我们在给予一氧化氮合酶抑制剂Nω - 硝基 - L - 精氨酸甲酯（L - NAME）之前和之后通过吸入给予异他林（20毫克）。静脉注射L - NAME（30毫克/千克）使Qbr迅速下降至基线值的约80%，而经吸入给予L - NAME（10毫克/千克）导致下降延迟且幅度较小（约22%）。通过两种给药途径用L - NAME预处理可减弱随后用异他林激发后的支气管动脉血管舒张。我们得出结论，吸入异他林以剂量依赖性方式增加Qbr，并且β - 激动剂诱导的支气管血管系统中血管平滑肌舒张部分是通过NO的合成介导的。
