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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1997-3-5
pubmed:abstractText
Nitric oxide (NO) is believed to mediate the phenomenon known as endothelium-dependent relaxation (EDR). NO synthase produces NO from its precursor, arginine (ARG). We have previously demonstrated impaired EDR in diabetic blood vessels. In this study, we investigated a possible mechanism for defective EDR in experimental diabetes and whether pancreatic islet transplantation could reverse established endothelial dysfunction. Streptozotocin-induced diabetic rats were maintained for 8 or 12 weeks. NO-mediated EDR was assessed in isolated thoracic rings ex vivo. A group of untreated diabetic rats received syngeneic islet transplantation at 8 weeks of diabetes and were tested for EDR after 4 weeks of euglycemia. EDR to acetylcholine was impaired in untreated diabetic rings. Endothelium-independent relaxation to nitroglycerin was unaltered. In vitro incubation of diabetic rings with 3 mM L-ARG (but not D-ARG) improved EDR to acetylcholine in rings from 8-week but not 12-week diabetic rats. L-ARG did not alter EDR in control rings nor relaxation to nitroglycerin in control or diabetic rings. Islet transplantation at 8 weeks of diabetes normalized blood glucose, plasma arginine and total glycosylated hemoglobin while restoring normal EDR. In conclusion, a defect in substrate/supply for NO synthesis is acutely reversed by ARG supplementation at early but not at later stages of diabetes. Also, preemptive surgical intervention with islet transplantation prior to the ARG-insensitive phase is an effective strategy to reverse established endothelial dysfunction in diabetes mellitus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0168-8227
pubmed:author
pubmed:issnType
Print
pubmed:volume
31 Suppl
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S157-62
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Restoration of vascular endothelial function in diabetes.
pubmed:affiliation
Department of Transplant Surgery, Medical College of Wisconsin Froedtert Memorial Hospital, Milwaukee 53226, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.