Increased pulmonary vascular contraction to serotonin after cardiopulmonary bypass: Role of cyclooxygenase

Background. Pulmonary vascular resistance is frequently elevated after card iopulmonary bypass (CPB). We examined if altered pulmonary microvascular re activity to serotonin (5-HT) is due to altered expression of isoforms of ni tric oxide synthase (NOS) or cyclooxygenase (COX), Materials and methods. Pigs (n = 8) were heparinized and placed on total CP B for 90 min and then perfused off CPB for 90 min. Noninstrumented pigs (n = 6) served as controls for vascular studies. Relaxation responses (% of pr econtraction) of microvessels (60-150 mu m in diameter) were examined in vi tro in a pressurized (20 mm Hg) no-flow state with video microscopic imagin g. Expression of eNOS, iNOS, and inducible (COX-2) and constitutive (COX-1) cyclooxygenase was examined with Western blotting and reverse transcriptio n polymerase chain reaction. Results. Pulmonary vascular resistance (PVR) increased from 316 +/- 39 mm H g x s/cm(5) at baseline to 495 +/- 53 at 60 min and 565 +/- 62 at 90 min af ter 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 c ontracted significantly to 5-HT (-29 +/- 27%, P < 0.05 vs control). This re sponse was partially inhibited (7 +/- 20%, P = 0.06) in the presence of the COX-2 inhibitor NS398, but was unaffected by the thromboxane synthase inhi bitor U63557A (-20 +/- 19%). Expression of iNOS or COX-1 was not changed af ter 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 hypercontr actile response of isolated pulmonary microvessels to 5-HT that was in part mediated by the release of prostaglandins (but not thromboxane) and associ ated with increased expression of COX-2 and with decreased expression of eN OS. (C) 2000 Academic Press.