Mechanisms underlying lysophosphatidylcholine-induced potentiation of vascular contractions in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat aorta

Abstract

Background and purpose:The effect of lysophosphatidylcholine (LPC) on aortic contractions in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetic model, was studied.Experimental approach:Using OLETF rats and control (Long Evans Tokushima Otsuka (LETO)) rats, the effects of LPC on the contractions induced by high-K + (10-40 mM), UK14,304 (10∼100 nM; a selective α 2-adrenoceptor agonist) and sodium orthovanadate (SOV; 10 μM∼3 mM) in endothelium-denuded aortae were compared. Aortic ERK activity and the mRNA expression for GPR4 (a putative LPC receptor) were also measured.Key results:OLETF rats exhibited (vs. age-matched LETO rats): (1) greater potentiation of high-K +-induced contraction by 10 μM LPC - a potentiation attenuated by 10 μM genistein, protein tyrosine kinase (PTK) inhibitor, (2) greater potentiation of UK14,304 (10∼100 nM)-induced contractions by LPC (1 μM∼10 μM) - a potentiation attenuated by 10 μM genistein, 50 μM tyrphostin A23 (PTK inhibitor) or 10 μM PD98059 (MEK 1/2 inhibitor), (3) greater basal and LPC (1 μM)-induced ERK activities, (4) greater basal and 100 nM UK14,304-stimulated ERK2 activities in both the absence and presence of 10 μM LPC, (5) greater SOV (10 μM∼3 mM)-induced contractions, (6) greater potentiation of SOV-induced contractions by 10 μM LPC - a potentiation suppressed by 10 μM PD98059 or 10 μM genistein, (7) upregulation of GPR4 mRNA.Conclusions and implications:These results suggest that the LPC-induced potentiation of contractions in the OLETF rat aorta may be attributable to increased PTKs or ERK activity and/or to receptor upregulation. © 2006 Nature Publishing Group All rights reserved.