why high BG affects blood vessels

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This article originally posted May 26, 2009 and appeared in

Issue 470

How High Blood Sugars Damage Blood Vessels

Researchers have gained fresh insights into how elevated glucose levels

damage blood vessels. The mechanism could lead to novel strategies for

blocking

the destruction.

High glucose levels reduce the levels of the powerful vasodilator nitric

oxide in blood vessels, a shortfall that increases the risk of high blood

pressure

and eventually narrows down the vessels.

Rita C. Tostes, physiologist in the MCG School of Medicine, found that

decreased ability of blood vessels to relax resulted from increased activity

of

a natural mechanism for altering protein form and function.

The researchers suspect that increased modification of proteins by a

glucose-derived molecule is a player in vascular problems associated with

hypertension,

stroke and obesity as well.

Tostes stated that, " We know diabetes is a major risk factor for

cardiovascular disease and we think this is one of the reasons. "

In the study conducted on healthy mice, the researchers found that there was

an increased activity by O-GlcNAc in the blood vessels, which competes with

another mechanism for modifying proteins called phosphorylation.

In blood vessels, phosphorylation modifies the enzyme that produces nitric

oxide, called nitric oxide synthase, so that it makes more of the blood

vessel

dilator.

O-GlcNAc seems to beat phosphorylation to the punch so there is the opposite

result.

Victor Lima, a graduate student at the University of Sao o working with

Dr. Tostes stated that, " The longer O-GlcNAc levels were high, the worse the

resulting problem. "

An animal model of hypertension confirmed the finding that the more

O-GlcNAc, the more blood vessels contract because these animals had higher

O-GlcNAc

levels.

" Now we are trying to see why this is happening and what comes first. Is

increased blood pressure leading to changed O-GlcNAc or are augmented levels

of

O-GlcNAc contributing to the change we see in the vasculature of

hypertensives? " said Dr. Tostes.

" If we know how this changes vascular function, we can understand some of

the dysfunction that we see in diabetes, " she added.

The study was presented at American Society of Hypertension 24th Annual

Scientific Program in San Francisco. May 2009

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