title: The role of aquaporin 1 activated by cGMP in myocardial edema caused by cardiopulmonary bypass in sheep.
abstract: OBJECTIVE
  Most cardiac procedures involve the use of cardiopulmonary bypass (CPB), which pumps oxygenated blood to the body while the heart and lungs are isolated. CPB can cause profound alterations V in the homeostasis of physiological fluids, which often results in myocardial edema. In our study, we used sheep CPB model of in vivo and in vitro to assess the relationship between cGMP and AQP1 during CPB.
  
  
  METHODS
  ODQ, a specific inhibitor of soluble guanylate cyclase (sGC), was used to treat the CPB animals or cardiomyocytes. Left ventricular function of each group was determined by pressure-volume system. Water content of myocardial tissue was assessed by dry-wet weight, and cardiomyocytes water permeability was also calculated. The concentration of cGMP was determined by Radioimmunoassay (RIA). mRNA and protein expression of AQP1 were detected by real-time PCR and western blot, respectively.
  
  
  RESULTS
  The relative expression level of AQP1 mRNA and protein at each time point (0, 6, 12, 24 or 48 h) after CPB was significantly increased (1.18-fold at 12 h, 1.77-fold at 24 h and 2.18-fold at 48h) compared with each sham group, the protein expression of AQP1 also showed a rising trend after CPB. The degree of myocardial edema (75.1% at 12 h, 79.3% at 24 h and 81.0% at 48h) increased following the CPB surgery. The mRNA expression level of AQP1 was significantly decreased by 39.7% (p<0.01) upon treatment with ODQ compared with the CPB-only group, and inhibition of cGMP pathway also can significantly decrease the degree of myocardial edema (84.7% in control group, while 75.2% in ODQ group) and improve cardiac function in sheep after CPB. Results of in vitro experiments showed the same changing trends as in vivo.
  
  
  CONCLUSIONS
  cGMP pathway controls water channels and then affects water intake during CPB through an AQP1-mediated pathway.
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Fang-bao
authors.initials: FB
authors.lastname: Ding
authors.forename: Yu-mei
authors.initials: YM
authors.lastname: Yan
authors.forename: Chun-rong
authors.initials: CR
authors.lastname: Bao
authors.forename: Jian-bing
authors.initials: JB
authors.lastname: Huang
authors.forename: Ju
authors.initials: J
authors.lastname: Mei
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.forename: Jun-wen
authors.initials: JW
authors.lastname: Zhang
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000502:physiology*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004489:Edema, Cardiac / Q000209:etiology* / Q000378:metabolism; D005260:Female; D032383:Myocytes, Cardiac / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D034561:Sheep, Domestic
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D010069:Oxadiazoles; D011810:Quinoxalines; D051398:Aquaporin 1; D006152:Cyclic GMP