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).

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 μm 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.

Pulmonary vascular resistance (PVR) increased from 316 ± 39 mm Hg × s/cm⁵ 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%.

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.