Relationship between phospholipase D activation and endothelial vasomotor dysfunction in rabbit aorta |
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Authors: | DA Cox ML Cohen |
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Affiliation: | Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 47628, USA. |
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Abstract: | Lysophosphatidylcholine (lysoPC) causes endothelial vasomotor dysfunction in isolated blood vessels, although the signaling pathways involved in this effect remain to be established. Although lysoPC stimulated phospholipase D (PLD) activity in cultured endothelial cells, the role of PLD in the vascular effects of lysoPC remains unclear. This study investigated the hypothesis that PLD is involved in lysoPC-induced endothelial vasomotor dysfunction in isolated rabbit aorta. LysoPC (3-30 microM) stimulated vascular PLD activity and inhibited endothelium-dependent vasorelaxation to acetylcholine within an identical concentration range. In contrast, lysoPC-induced inhibition of vasorelaxation was not prevented by the selective protein kinase C (PKC) inhibitor, GF109203X (3 microM), which suggested that this enzyme was not involved in the endothelial vasomotor dysfunction produced by lysoPC. The ability of two other lysophospholipids, lyso-platelet-activating factor (3-30 microM) and lysophosphatidylserine (10-30 microM) to induce endothelial vasomotor dysfunction was also associated closely with their ability to stimulate vascular PLD activity. Parallel stimulation of PLD activity and inhibition of acetylcholine-induced relaxation was also observed with orthovanadate (0.1-3 mM), which suggested that the association between PLD activation and endothelial vasomotor dysfunction was not a phenomenon particular to lysophospholipids. The magnitude of PLD stimulation and the extent of endothelial dysfunction induced by these diverse stimuli were highly correlated (r2 = 0.88). These observations suggest that the PLD signal transduction pathway is important in the endothelial vasomotor dysfunction produced by lysophospholipids and perhaps other agents. |
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