title: Altered coronary microvascular serotonin receptor expression after coronary artery bypass grafting with cardiopulmonary bypass.
abstract: OBJECTIVE
  We evaluated roles of serotonin 1B and 2A receptors, thromboxane synthase and receptor, and phospholipases A(2) and C in response to cardiopulmonary bypass.
  
  
  METHODS
  Patients' atrial tissues were harvested before and after cardiopulmonary bypass with cardioplegia (n = 13). Coronary microvessels were assessed for vasoactive response to serotonin with and without inhibitors of serotonin 1B and 2A receptors and phospholipases A(2) and C. Expressions of serotonin receptor messenger RNA were determined with reverse transcriptase polymerase chain reaction. Expressions of serotonin receptors and thromboxane A(2) receptor and synthase proteins were determined with immunoblotting and immunohistochemistry.
  
  
  RESULTS
  Microvessel exposure to serotonin elicited 7.3% +/- 2% relaxation before bypass, changing to contraction of -19.2% +/- 2% after bypass (P <.001). Additions of specific serotonin 1B receptor antagonist and inhibitor of phospholipase A(2) resulted in significantly decreased contraction, -8.6% +/- 1% (P < .001) and 2.8% +/- 3% (P = .001), respectively. Serotonin 1B receptor messenger RNA expression increased 1.82 +/- 0.34-fold after bypass (p = .044); serotonin 2A receptor messenger RNA expression did not change. Serotonin 1B but not 2A receptor protein expression increased after bypass by 1.35 +/- 0.7-fold (P = .0413). Thromboxane synthase and receptor expressions were unchanged after bypass. Serotonin 1B receptor increased mainly in arterial smooth muscle. There were no appreciable differences in arterial expressions of thromboxane synthase or receptor.
  
  
  CONCLUSIONS
  Serotonin-induced vascular dysfunction after cardiopulmonary bypass with cardioplegic arrest may be mediated by increased expression of serotonin 1B receptor and subsequent phospholipase A(2) activation in myocardial coronary smooth muscle.
authors: Department of Surgery, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors: Michael P
authors: MP
authors: Robich
authors: Eugenio G
authors: EG
authors: Araujo
authors: Jun
authors: J
authors: Feng
authors: Robert M
authors: RM
authors: Osipov
authors: Richard T
authors: RT
authors: Clements
authors: Cesario
authors: C
authors: Bianchi
authors: Frank W
authors: FW
authors: Sellke
mesh_terms: D000368:Aged; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003331:Coronary Vessels / Q000378:metabolism*; D006324:Heart Arrest, Induced / Q000009:adverse effects; D006325:Heart Atria / Q000378:metabolism*; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D054467:Phospholipases A2 / Q000096:biosynthesis; D011184:Postoperative Period; D044302:Receptor, Serotonin, 5-HT1B / Q000096:biosynthesis; D044402:Receptor, Serotonin, 5-HT2A / Q000096:biosynthesis; D011985:Receptors, Serotonin / Q000096:biosynthesis*; D017482:Receptors, Thromboxane / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000096:biosynthesis; D010738:Type C Phospholipases / Q000096:biosynthesis; D014652:Vascular Diseases / Q000209:etiology / Q000503:physiopathology*; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D017482:Receptors, Thromboxane; D054467:Phospholipases A2; D010738:Type C Phospholipases; D013930:Thromboxane-A Synthase