Lysophosphatidylcholine Potentiates Phenylephrine Responses in Rat Mesenteric Arterial Bed through Modulation of Thromboxane A₂

Abstract

Lysophosphatidylcholine (LPC) plays important physiological and pathophysiological roles in the cardiovascular system. Despite this, there is little information about its effects on vasoreactivity of resistance vessels. The present study was designed to characterize the effects of LPC in the isolated perfused rat mesenteric arterial bed (MAB) and to investigate the underlying mechanisms of the changes it produced. Perfusion with 10 M LPC for 40 min did not significantly affect basal perfusion pressure or reactivity of MAB to the ␣ 1 -adrenoceptor agonist phenylephrine (PE) but almost completely abolished the maximal endothelium-dependent relaxation to acetylcholine (Ach), reducing it from 93 Ϯ 5 to 7 Ϯ 4% (p Ͻ 0.001). After washout of LPC for 60 min, the vasodilator response to Ach partially recovered, whereas the vasoconstrictor response to PE was markedly enhanced, the pD 2 value increasing from 7.50 Ϯ 0.04 to 8.13 Ϯ 0.15 and maximum response to 199 Ϯ 24% of control (p Ͻ 0.001). Pretreatment with either indomethacin, a nonselective inhibitor of cyclooxygenase, or SQ-29548 [[1S-[1a,2a(Z), a selective thromboxane receptor antagonist, completely prevented the potentiation of the PE response after washout of LPC. In untreated MABs, only the highest concentration of PE produced a significant increase in thromboxane A 2 (TxA 2 ) production (assessed by enzyme-immunoassay of thromboxane B 2 levels). This was prevented by perfusion with LPC but was significantly increased after LPC washout. The basal release of TxA 2 was not modified by LPC. These results demonstrate that LPC exerts both immediate and residual effects on the reactivity of the rat MAB and that these effects are at least partially due to modification of PE-induced TxA 2 production.

Lysophosphatidylcholine is Generated by Spontaneous Deacylation of Oxidized Phospholipids

“…LysoPC is an important major lysophospholipid that is generated as a breakdown product of lipoprotein PCs. This production of lysoPC has been considered to be a result of endogenous phospholipase A 2 (PLA 2 ) activation (2). Present in the cell membranes or the polar surface of oxidized lipoproteins, lysoPC plays important physiological and pathophysiological roles including vascular development, reproduction, myelination, neuronal diseases, and cancer in both humans and animals.…”