Pearse D B, Becker P M
Department of Medicine, Division of Pulmonary and Critical Care Medicine, The Johns Hopkins Medical Institutions at the Asthma and Allergy Center, Hopkins Bayview Medical Center, Baltimore, Maryland 21224, USA.
Am J Physiol Heart Circ Physiol. 2000 Nov;279(5):H2077-84. doi: 10.1152/ajpheart.2000.279.5.H2077.
We previously found that increased intravascular pressure decreased ischemic lung injury by a nitric oxide (NO)-dependent mechanism (Becker PM, Buchanan W, and Sylvester JT. J Appl Physiol 84: 803-808, 1998). To determine the role of cyclic nucleotides in this response, we measured the reflection coefficient for albumin (sigma(alb)), fluid flux (), cGMP, and cAMP in ferret lungs subjected to either 45 min ("short"; n = 7) or 180 min ("long") of ventilated ischemia. Long ischemic lungs had "low" (1-2 mmHg, n = 8) or "high" (7-8 mmHg, n = 6) vascular pressure. Other long low lungs were treated with the NO donor (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium -1, 2-diolate (PAPA-NONOate; 5 x 10(-4) M, n = 6) or 8-bromo-cGMP (5 x 10(-4) M, n = 6). Compared with short ischemia, long low ischemia decreased sigma(alb) (0.23 +/- 0.04 vs. 0.73 +/- 0.08; P < 0.05) and increased (1.93 +/- 0.26 vs. 0.58 +/- 0.22 ml. min(-1). 100 g(-1); P < 0.05). High pressure prevented these changes. Lung cGMP decreased by 66% in long compared with short ischemia. Lung cAMP did not change. PAPA-NONOate and 8-bromo-cGMP increased lung cGMP, but only 8-bromo-cGMP decreased permeability. These results suggest that ischemic vascular injury was, in part, mediated by a decrease in cGMP. Increased vascular pressure prevented injury by a cGMP-independent mechanism that could not be mimicked by administration of exogenous NO.
我们之前发现，血管内压力升高可通过一氧化氮（NO）依赖机制减轻缺血性肺损伤（Becker PM、Buchanan W和Sylvester JT。《应用生理学杂志》84: 803 - 808，1998年）。为了确定环核苷酸在此反应中的作用，我们测量了雪貂肺脏在经历45分钟（“短时间”；n = 7）或180分钟（“长时间”）通气缺血后的白蛋白反射系数（σ(alb)）、液体通量（）、cGMP和cAMP。长时间缺血的肺脏具有“低”（1 - 2 mmHg，n = 8）或“高”（7 - 8 mmHg，n = 6）血管压力。其他长时间处于低压力的肺脏用NO供体（Z）-1-[N - （3 - 氨丙基）-N - （正丙基）氨基]重氮 - 1，2 - 二醇盐（PAPA - NONOate；5×10⁻⁴ M，n = 6）或8 - 溴 - cGMP（5×10⁻⁴ M，n = 6）进行处理。与短时间缺血相比，长时间低压力缺血降低了σ(alb)（0.23±0.04对0.73±0.08；P < 0.05）并增加了（1.93±0.26对0.58±0.22 ml·min⁻¹·100 g⁻¹；P < 0.05）。高压可防止这些变化。与短时间缺血相比，长时间缺血时肺脏cGMP降低了66%。肺脏cAMP未发生变化。PAPA - NONOate和8 - 溴 - cGMP增加了肺脏cGMP，但只有8 - 溴 - cGMP降低了通透性。这些结果表明，缺血性血管损伤部分是由cGMP降低介导的。血管压力升高通过一种不依赖cGMP的机制防止损伤，这种机制不能通过给予外源性NO来模拟。
