Hyperglycemia is involved in the dysregulation of endothelial nitric oxide (NO) synthase, leading to endothelial dysfunction and an increased risk of vasculopathy, said Markku Laakso, MD.
Hyperglycemia is involved in the dysregulation of endothelial nitric oxide (NO) synthase, leading to endothelial dysfunctionand an increased risk of vasculopathy, said Markku Laakso, MD.
He discussed the NO pathway of endothelial function. A healthy endothelium has sufficient NO bioavailability to prevent ordampen the effects of reactive oxygen species, inflammation, leukocyte margination, platelet aggregation, vascular smoothmuscle proliferation, and vasoconstriction. Diabetes is associated with a lack of NO bioavailability to counterbalance theinsults to the endothelium.
A reduction in NO bioavailability and therefore an inability to deliver blood flow and/or oxygen to tissues is responsiblefor a reduction in acute exercise capacity in subjects with diabetes.
Nitrite is a biochemical marker of endothelial health. Plasma nitrite reflects acute and chronic changes in endothelial NOsynthase activity and serves as a donor of NO.
Research has demonstrated a relationship between peak forearm-mediated dilation (FMD) in the brachial artery and plasmalevels of nitrite, which suggests that brachial FMD and/or plasma nitrite are markers of peripheral endothelialfunction.
Exercise significantly increases plasma nitrite in healthy individuals or subclinical vascular disease, but there is a netreduction in plasma nitrite following exercise in subjects with cardiovascular disease. "An inability to increase plasmanitrite flux following chronic exercise discriminates subclinical diabetes mellitus from other risk factors," said Dr.Laakso, academy professor, department of medicine, University of Kuopio, Finland.
Hb-A1c may actually bemediator of vascular disease
Hemoglobin A1c may actually be a mediator of vascular disease than just a marker, he said. The red blood cell (RBC) isrecognized as a transporter and promoter of NO release within the cardiovascular system. The function of the RBC to releaseNO can be inhibited by diabetes; diabetes causes RBC glycation and alteration of structure, altered RBC-NO metabolism thatyields a deficiency in the release of vasodilators, reduced vascular function, and finally, vasculopathy.
Targets for treatment to improve endothelial function based on the NO pathway are still years away, he said.