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

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.

[Relationship between gut microbiota-derived substances and vascular function: focus on indoxyl sulfate and trimethylamine-N-oxide].

Emerging evidences suggest that gut microbiota-derived substances play a pivotal role in the regulation of host homeostasis including vascular function. Actually, these substances and/or their metabolites can be presented in circulation and local tissue and their levels are often abnormal in the pathophysiological states. Therefore, to determine the role of them in physiological function is important in human health. On the other hand, vascular dysfunction is a key event in the initiation and progression of systematic complications of cardiovascular, kidney and metabolic diseases including hypertension, dyslipidemia, diabetes, and atherosclerosis. Although abnormalities in endothelial and vascular smooth muscle cells play an important role on vascular dysfunction, emerging evidences has suggested that gut microbiota-derived substances can directly or indirectly affect these cellular functions. The present review will focus on the relationship between vascular function and indoxyl sulfate or trimethylamine-N-oxide (TMAO).