Mechanisms underlying the methylglyoxal-induced enhancement of uridine diphosphate-mediated contraction in rat femoral artery

Abstract

Although femoral artery dysfunctions, including aberrant vascular reactivity to vasoactive substances, are common in many chronic disorders, such as diabetes and hypertension, their inducible and/or progressive factors remain unclear. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, has been implicated in the pathogenesis of various chronic disorders. However, its direct correlation with extracellular nucleotides including uridine 5′-diphosphate (UDP) in the femoral artery function is currently unknown. Therefore, we investigated the acute effect of MGO on UDP-induced contraction in the rat femoral artery. MGO (4.2 × 10−4 M for 1 h) enhanced the UDP-induced contraction. This enhancement was not abolished in all conditions, including nitric oxide synthase inhibition, cyclooxygenase inhibition, or endothelial denudation. In the endothelium-denuded arteries, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (10−5 M) suppressed the UDP-induced contraction in both control and MGO-treated groups, while MGO enhanced the p38 MAPK activation regardless of the UDP presence. Moreover, in the endothelium-denuded arteries, the Syk tyrosine kinase inhibitor piceatannol (10−5 M) suppressed the UDP-induced contraction. These results suggest that MGO augments UDP-induced contraction in rat femoral arteries and that this may be partly due to the alterations in the activities of Syk tyrosine kinase and p38 MAPK in the smooth muscle.