title: [Endogenous nitric oxide pathway in high pulmonary blood flow-induced pulmonary vascular structural remodeling].
abstract: OBJECTIVE
  Pulmonary vascular structural remodeling induced by high pulmonary blood flow is an important pathologic basis of pulmonary hypertension with congenital heart disease of left-to-right shunt. However, the mechanism is still not clear. The present study aimed to examine the alteration of endogenous nitric oxide (NO) pathway in high pulmonary blood flow-induced pulmonary vascular structural remodeling, so as to explore the role of NO pathway in pulmonary hypertension induced by high pulmonary blood flow.
  
  
  METHODS
  Sixteen male SD rats were randomly divided into control group (n = 8) and shunting group (n = 8). Aortocaval shunting was produced for 11 weeks in shunt rats. Pulmonary artery mean pressure (mPAP) of each rat was evaluated using right cardiac catheterization. The ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV + S)] was detected. Pulmonary vascular micro-and ultra-structure was examined by using a light microscope and a transmitted electronic microscope. Meanwhile, the concentration of plasma NO was measured by spectrophotometry. The expressions of endothelial NO synthase (eNOS) mRNA and protein by pulmonary arteries were detected by in situ hybridization and immunohistochemistry, respectively.
  
  
  RESULTS
  After 11-week aortocaval shunting, mPAP was significantly increased [(22.5 +/- 2.6) mmHg vs. (15.8 +/- 2.8) mmHg, 1 mmHg = 0.133 kPa, t = 4.97, P < 0.01], and RV/(LV + S) was also markedly increased (0.267 +/- 0.022 vs. 0.221 +/- 0.016, t = 4.85, P < 0.01). The percentage of muscularized arteries was obviously increased in shunt rats compared with controls [(23.2 +/- 2.4)% vs. (13.5 +/- 2.1)%, t = 7.82, P < 0.01], and relative medial thickness of pulmonary arteries was obviously increased in shunt rats [median pulmonary artery: (7.76 +/- 0.56)% vs. (4.82 +/- 1.03)%, t = 6.23, P < 0.01; small pulmonary artery: (11.94 +/- 0.66)% vs. (6.91 +/- 0.53)%, t = 14.96, P < 0.01]. Ultrastructural changes, such as hyperplasia and degeneration of endothelial cells, irregularity of internal elastic laminar and hypertrophy and the increased number of synthetic phenotype of smooth muscle cells, were found in intrapulmonary arteries of shunt rats. Meanwhile, plasma NO concentration was increased [(30.2 +/- 7.9) micromol/L vs (19.7 +/- 5.7) micromol/L, t = 3.05, P < 0.01) and eNOS mRNA and protein expressions by pulmonary arteries were significantly augmented in rats of shunting group.
  
  
  CONCLUSIONS
  The upregulation of eNOS/NO might be an adaptive response of pulmonary circulation to an increased blood flow in the development of pulmonary hypertension and pulmonary vascular structural remodeling.
authors.affiliation: Department of Pediatrics, First Hospital of Peking University, Beijing 100034, China.
authors.forename: Jian-guang
authors.initials: JG
authors.lastname: Qi
authors.forename: Jun-bao
authors.initials: JB
authors.lastname: Du
authors.forename: Xiu-ying
authors.initials: XY
authors.lastname: Tang
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Wei
authors.forename: Chao-shu
authors.initials: CS
authors.lastname: Tang
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000097:blood* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D011651:Pulmonary Artery / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat