Altered coronary microvascular serotonin receptor expression after coronary artery bypass grafting with cardiopulmonary bypass.

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.