title: Cavopulmonary anastomosis induces pulmonary expression of the angiotensin II receptor family.
abstract: BACKGROUND
  Cavopulmonary anastomosis is used for palliation of cyanotic cardiac lesions. Postoperative development of pulmonary arteriovenous malformations can be significant in 10% to 25% of patients. To study the basis for formation of arteriovenous malformations, we developed an ovine model that reliably induces their development 8 weeks after cavopulmonary anastomosis. Previously, we found that cavopulmonary anastomosis inhibits the expression of pulmonary angiotensin-converting enzyme and suppresses angiotensin II production.
  
  
  OBJECTIVE
  This study examines the role of the angiotensin II receptors, type 1 and type 2, in this setting of pulmonary vascular remodeling.
  
  
  METHODS
  Lambs, aged 40 to 50 days, underwent cavopulmonary anastomosis. In age-matched control animals, a sham operation was performed. Messenger RNA and protein expression in lung specimens was measured at successive time points after cavopulmonary anastomosis or sham operations (n = 3 at each time point).
  
  
  RESULTS
  Angiotensin type 1 mRNA was maximally upregulated 2-fold at 5 weeks after cavopulmonary anastomosis (P =.006). Expression of angiotensin type 1 protein was increased at least 2-fold at 2, 5, and 15 weeks after cavopulmonary anastomosis (P =.005). Cavopulmonary anastomosis also increased angiotensin type 2 mRNA and protein expression at least 2-fold at 2 and 5 weeks (P =.02) after surgical intervention. At 15 weeks, expression of angiotensin type 2 mRNA and protein was unchanged from that seen in control animals. Immunolocalization in pulmonary tissue sections 2 weeks after cavopulmonary anastomosis revealed markedly enhanced staining of angiotensin II receptor type 1 in vascular smooth muscle and angiotensin II receptor type 2 in the endothelium of pulmonary arteries.
  
  
  CONCLUSIONS
  Rapid elevation in the expression of the type 1 and 2 angiotensin II receptors in the affected pulmonary vasculature after cavopulmonary anastomosis suggests their involvement in the pathologic vascular remodeling that occurs after cavopulmonary anastomosis.
authors: Division of Cardiothoracic Surgery, University of California, San Francisco 94305-5407, USA.
authors: Sunil P
authors: SP
authors: Malhotra
authors: V Mohan
authors: VM
authors: Reddy
authors: Stephan
authors: S
authors: Thelitz
authors: You-Ping
authors: YP
authors: He
authors: Frank L
authors: FL
authors: Hanley
authors: Sam
authors: S
authors: Suleman
authors: R Kirk
authors: RK
authors: Riemer
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism; D015870:Gene Expression; D018610:Heart Bypass, Right; D007150:Immunohistochemistry; D023421:Models, Animal; D008955:Models, Cardiovascular; D011651:Pulmonary Artery / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000096:biosynthesis* / Q000235:genetics; D012756:Sheep; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin