title: Increased pulmonary vascular contraction to serotonin after cardiopulmonary bypass: role of cyclooxygenase.
abstract: BACKGROUND
  Pulmonary vascular resistance is frequently elevated after cardiopulmonary bypass (CPB). We examined if altered pulmonary microvascular reactivity to serotonin (5-HT) is due to altered expression of isoforms of nitric oxide synthase (NOS) or cyclooxygenase (COX).
  
  
  METHODS
  Pigs (n = 8) were heparinized and placed on total CPB for 90 min and then perfused off CPB for 90 min. Noninstrumented pigs (n = 6) served as controls for vascular studies. Relaxation responses (% of precontraction) of microvessels (60-150 microm in diameter) were examined in vitro in a pressurized (20 mm Hg) no-flow state with video microscopic imaging. Expression of eNOS, iNOS, and inducible (COX-2) and constitutive (COX-1) cyclooxygenase was examined with Western blotting and reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Pulmonary vascular resistance (PVR) increased from 316 +/- 39 mm Hg x s/cm(5) at baseline to 495 +/- 53 at 60 min and 565 +/- 62 at 90 min after termination of CPB. 5-HT elicited a relaxation response (46.8 +/- 11. 8%) in precontracted control microvessels. This response was not affected by the NOS inhibitor N(G)-nitro-l-arginine. After CPB, pulmonary microvessels contracted significantly to 5-HT (-29 +/- 27%, P < 0.05 vs control). This response was partially inhibited (7 +/- 20%, P = 0.06) in the presence of the COX-2 inhibitor NS398, but was unaffected by the thromboxane synthase inhibitor U63557A (-20 +/- 19%). Expression of iNOS or COX-1 was not changed after CPB. Protein and mRNA expressions of COX-2 both increased significantly after CPB, while that of eNOS decreased by approximately 50%.
  
  
  CONCLUSIONS
  PVR increased after CPB. This was associated with a hypercontractile response of isolated pulmonary microvessels to 5-HT that was in part mediated by the release of prostaglandins (but not thromboxane) and associated with increased expression of COX-2 and with decreased expression of eNOS.
authors.affiliation: Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Boston, Massachusetts 02215, USA.
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Metais
authors.forename: C
authors.initials: C
authors.lastname: Bianchi
authors.forename: F
authors.initials: F
authors.lastname: Sellke
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000201:enzymology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009599:Nitroprusside / Q000494:pharmacology; D011183:Postoperative Complications / Q000188:drug therapy / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; D007527:Isoenzymes; D014665:Vasodilator Agents; D009599:Nitroprusside; D012701:Serotonin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases