[PHNUTR-L] Diabetes makes it hard for blood vessels to relax

[Kathrynne Holden]

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Public release date: 31-Jan-2008
http://www.eurekalert.org/pub_releases/2008-01/mcog-dmi013108.php

Contact: Toni Baker
tbaker at mcg.edu
706-721-4421
Medical College of Georgia

Diabetes makes it hard for blood vessels to relax

One way diabetes is bad for your blood vessels is by creating too much 
competition for an amino acid that helps blood vessels relax, 
researchers say.

That amino acid, L-arginine, is broken down by the enzyme arginase to 
urea, which helps the body eliminate toxins resulting from the proteins 
we eat. Diabetics have a lot of arginase activity, which means they use 
a lot more L-arginine, says Dr. Maritza Romero, postdoctoral fellow at 
the Medical College of Georgia and lead author of the paper published in 
the current issue of Circulation Research.

It also means too little L-arginine is available to help nitric oxide 
synthase make nitric oxide, the powerful vasodilator that helps blood 
vessels relax, says Dr. Romero, who works in the lab of Dr. R. William 
Caldwell, chair of the MCG Department of Pharmacology and Toxicology and 
the study’s corresponding author.

Researchers also found the amino acid, L-citrulline, as well as statins, 
compounds known to lower cholesterol, prevent elevation of arginase 
activity, restoring normal dilation abilities in animal models of type 1 
diabetes. In fact, L-citrulline can be recycled into L-arginine.

Now they want to know specific factors and pathways involved in arginase 
activation and develop pharmaceutical agents to combat excessive 
arginase activity in diabetes. They also suggest clinical trials of 
L-citrulline as a supplemental therapy for diabetics with vascular problems.

Their findings also help explain why L-arginine supplement, marketed to 
treat hypertension, chest pain, heart failure and more, may not work 
long term. In the January 4, 2006 issue of the Journal of the American 
Medical Association, Johns Hopkins researchers reported that a clinical 
trial of patients taking an L-arginine supplement following a heart 
attack didn’t improve in their vascular tone or their hearts’ ability to 
pump. In fact, more patients died who were taking L-arginine than 
placebo and the study was closed with the recommendation the supplement 
not be used by heart attack patients. The supplement still is widely 
marketed.

“The findings of increased arginase I activity in diabetes may limit 
other therapeutic approaches proposed for early endothelial dysfunction 
such as oral L-arginine supplementation,” Drs. Thomas L. Luscher and Jan 
Steffel, of the University of Zurich Cardiovascular Research Institute 
write in an accompanying editorial. “Although dietary L-arginine 
supplementation has been shown to exert vascular protective effects in 
certain clinical settings, this approach is unlikely to be effective in 
diabetes, if the results of this study can be confirmed by patients in 
vivo. In fact, the findings of Romera et al may provide a possible 
explanation for the unexpected neutral or even adverse effects of oral 
L-arginine in some clinical studies, in particular patients with 
coronary artery disease and infarction.”

A short intravenous course of L-arginine may provide short-term 
improvement in blood vessel tone, Dr. Romero notes. However most of 
L-arginine ingested goes directly to the liver to be broken down, not 
the bloodstream where it can promote relaxation of blood vessels, Dr. 
Romero says.

Arginase also is associated with vascular problems related to aging, 
hypertension, sickle cell disease, atherosclerosis and erectile 
dysfunction, Dr. Romero says. L-citrulline already is taken by some 
sickle cell patients to reduce breath-taking fibrosis in their lungs. In 
addition to helping the body turn toxins into urea that can be safely 
eliminated from the body, arginase also helps in collagen formation and 
cell proliferation, but too much can be bad. In fact, Drs. Caldwell and 
Romero are pursuing studies of how increased arginase activity may 
harden blood vessel walls.
-- 
Kathrynne Holden, MS, RD < fivestar at nutritionucanlivewith.com >
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