Seibert A F, Thompson W J, Taylor A, Wilborn W H, Barnard J, Haynes J
Department of Medicine, College of Medicine, University of South Alabama, Mobile 36617.
J Appl Physiol (1985). 1992 Jan;72(1):389-95. doi: 10.1152/jappl.1992.72.1.389.
Ischemia-reperfusion (IR) is a form of oxidant injury known to increase microvascular permeability in the lung. Agents that increase adenosine 3',5'-cyclic monophosphate (cAMP) levels have been shown to have beneficial effects in several models of oxidant lung injury associated with increased microvascular permeability. We investigated the role of adenylate cyclase activation with isoproterenol (ISO) or forskolin (FSK) in reversing the increased microvascular permeability associated with IR. ISO or FSK administered after 45 min of ischemia and 46 min of reperfusion caused a reduction in the capillary filtration coefficient (Kfc) from 1.25 +/- 0.13 to 0.53 +/- 0.08 and 0.55 +/- 0.10 ml.min-1.cmH2O-1.100 g tissue-1, respectively, at 90 min of reperfusion. This reduction in Kfc was accompanied by a rise in perfusate cAMP levels from 16.5 +/- 4.9 and 31.2 +/- 11.9 pmol/ml at 45 min of reperfusion to 444.2 +/- 147.8 and 276.1 +/- 91.0 pmol/ml at 105 min of reperfusion in lungs treated with ISO or FSK, respectively, at 46 min of reperfusion. Dibutyryl cAMP (DBcAMP), a membrane-permeable cAMP analogue, mimicked the permeability effect by reducing Kfc to 0.67 +/- 0.15 at 90 min of reperfusion. Significant hemodynamic changes occurred but were small and cannot explain the observed effect on Kfc. Photomicrographs from lungs treated with ISO or FSK revealed a reversal of the morphological manifestations of increased microvascular permeability. We conclude that the increased microvascular permeability associated with IR can be reversed by ISO, FSK, and DBcAMP and that cAMP produced by the lung contributes to the observed reversal.
缺血再灌注（IR）是一种已知会增加肺部微血管通透性的氧化损伤形式。已证明，提高3',5'-环磷酸腺苷（cAMP）水平的药物在几种与微血管通透性增加相关的氧化型肺损伤模型中具有有益作用。我们研究了用异丙肾上腺素（ISO）或福斯可林（FSK）激活腺苷酸环化酶在逆转与IR相关的微血管通透性增加方面的作用。在缺血45分钟和再灌注46分钟后给予ISO或FSK，在再灌注90分钟时，毛细血管滤过系数（Kfc）分别从1.25±0.13降至0.53±0.08和0.55±0.10 ml·min⁻¹·cmH₂O⁻¹·100 g组织⁻¹。Kfc的这种降低伴随着灌注液cAMP水平的升高，在用ISO或FSK处理的肺中，在再灌注46分钟时，再灌注45分钟时的灌注液cAMP水平分别为16.5±4.9和31.2±11.9 pmol/ml，到再灌注105分钟时分别升至444.2±147.8和276.1±91.0 pmol/ml。二丁酰cAMP（DBcAMP），一种可透过膜的cAMP类似物，通过在再灌注90分钟时将Kfc降至0.67±0.15来模拟通透性效应。发生了显著的血流动力学变化，但变化很小，无法解释观察到的对Kfc的影响。用ISO或FSK处理的肺的显微照片显示微血管通透性增加的形态学表现得到了逆转。我们得出结论，与IR相关的微血管通透性增加可被ISO、FSK和DBcAMP逆转，并且肺产生的cAMP有助于观察到的逆转。
