A model to study physiological activation of phospholipase A sub 2 and vasorelaxation by lysophosphatidylcholine

Earlier we demonstrated that micellar solutions of LPC caused endothelium-dependent relaxation of rabbit thoracic aorta and bovine intrapulmonary artery and vein through a cyclic GMP-dependent mechanism. The availability of LPC for vasorelaxation depends on its production by deacylation of PC by PLA{sub 2}. We assessed the possible activation of PLA{sub 2} by commonly used vasorelaxants such as acetylcholine, bradykinin, calcium ionophore A23187 and thrombin and vasoconstrictors like histamine and phenylephrine in the presence of indomethacin in a model system where {sup 14}C PC was incorporated into bovine intrapulmonary arterial segments. Taking the ratio of {sup 14}C PC:LPC formed by exogenous PLA{sub 2} as an index of deacylation, we found that while all the agents relaxed the strips in an endothelium-dependent manner, only thrombin caused relaxation followed by an increase in {sup 14}C LPC and a concomittant decrease in {sup 14}C PC indicating activation of PLA{sub 2}. Our data show that PC/PLA{sub 2} system can be activated to generate LPC for vascular relaxation under specific physiological conditions. This model system can be used to monitor PLA{sub 2} activity and LPC production to compensate flow and pressure induced changes in arteries.