Maclean M R, Johnston E D, Mcculloch K M, Pooley L, Houslay M D, Sweeney G
Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland.
J Pharmacol Exp Ther. 1997 Nov;283(2):619-24.
Phosphodiesterase (PDE) activity was determined in pulmonary arteries removed from control and chronic hypoxia-induced pulmonary hypertensive rats. The main, first-branch, intrapulmonary and resistance pulmonary arteries were studied. We measured total cAMP PDE activity and cGMP PDE activity, as well as that of individual isoforms (PDE1-5). cAMP PDE activity in chronic hypoxic rats was increased in first-branch and intrapulmonary arteries from hypoxic rats. No changes were observed in the main or resistance pulmonary arteries. Similarly, cGMP PDE activity was increased in the main, first-branch and intra-pulmonary arteries of the hypoxic rats. No changes in cGMP PDE activity were observed in resistance arteries. There was evidence for PDE1-5 activity in all pulmonary arteries. The increased cAMP PDE activity in first-branch and intrapulmonary vessels was associated with an increase in cilostimide-inhibited PDE (PDE3) activity. Increased total cGMP PDE in main pulmonary artery was associated with increases in Ca++/calmodulin-stimulated (PDE1) activity. An increase in zaprinast-inhibited (PDE5) activity was observed in first-branch and intrapulmonary arteries. Our results suggest that decreases in intracellular cyclic nucleotide levels in pulmonary arteries from pulmonary hypertensive rats are associated with increased PDE activity. Further, these changes may reflect alterations at the level of specific types of PDE isoforms.
在从对照大鼠和慢性低氧诱导的肺动脉高压大鼠中取出的肺动脉中测定磷酸二酯酶（PDE）活性。研究了主肺动脉、第一分支肺动脉、肺内动脉和阻力肺动脉。我们测量了总cAMP PDE活性、cGMP PDE活性以及各个同工型（PDE1 - 5）的活性。慢性低氧大鼠第一分支肺动脉和肺内动脉中的cAMP PDE活性增加。主肺动脉或阻力肺动脉中未观察到变化。同样，低氧大鼠的主肺动脉、第一分支肺动脉和肺内动脉中的cGMP PDE活性增加。阻力动脉中未观察到cGMP PDE活性变化。所有肺动脉中均有PDE1 - 5活性的证据。第一分支血管和肺内血管中cAMP PDE活性的增加与西洛司特抑制的PDE（PDE3）活性增加有关。主肺动脉中总cGMP PDE的增加与Ca++/钙调蛋白刺激的（PDE1）活性增加有关。在第一分支肺动脉和肺内动脉中观察到扎普司特抑制的（PDE5）活性增加。我们的结果表明，肺动脉高压大鼠肺动脉中细胞内环核苷酸水平的降低与PDE活性增加有关。此外，这些变化可能反映了特定类型的PDE同工型水平的改变。
