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CARDIOVASCULAR

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

Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada

Lysophosphatidylcholine (LPC) plays important physiological and pathophysiological roles in the cardiovascular system. Despite this, there is little information about its effects on vasore-activity 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 µM 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 ± 5 to 7 ± 4% (p < 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 pD₂ value increasing from 7.50 ± 0.04 to 8.13 ± 0.15 and maximum response to 199 ± 24% of control (p < 0.001). Pretreatment with either indomethacin, a nonselective inhibitor of cyclooxygenase, or SQ-29548 [[1S-[1a,2a(Z),3a,4a]]-7-[3-[[2-[(phenylamino)carbonyl]hydrazino] methyl]-7-oxabicyclo [2.2.1]hept-2-yl]-5-heptanoic acid], 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 A₂ (TxA₂) production (assessed by enzyme-immunoassay of thromboxane B₂ levels). This was prevented by perfusion with LPC but was significantly increased after LPC washout. The basal release of TxA₂ 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 TxA₂ production.

Address correspondence to: Dr. Kathleen M. MacLeod, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver V6T 1Z3, BC, Canada. E-mail: kmm{at}interchange.ubc.ca