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Horm Metab Res 2004; 36(5): 319-335
DOI: 10.1055/s-2004-814489
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

The Role of Nitric Oxide in the Development of Diabetic Angiopathy

F.  Santilli1 , F.  Cipollone1 , A.  Mezzetti1 , F.  Chiarelli1
  • 1Departments of Medicine and Pediatrics, University of Chieti, Italy
Further Information

Publication History

Received 9 April 2003

Accepted after Revision 3 December 2003

Publication Date:
24 May 2004 (online)

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Abstract

Diabetic angiopathy is the main cause of morbidity and mortality in patients with diabetes mellitus. Clinical manifestations and pathophysiological mechanisms of diabetic angiopathy can be traced back to the development of endothelial cell dysfunction with alterations in the eNOS/NO system production or availability as the primum movens in its natural history. Hyperglycemia per se or through the accumulation of AGEs, increased oxidative stress, leading to NOS uncoupling and NO-quenching by excess superoxide and peroxynitrite, and individual genetic background are thought to be responsible for this NO metabolism imbalance. The complex interplay of these mechanisms results in a perturbation of the physiological properties of NO in the maintenance of endothelial homeostasis, such as vasodilation, anticoagulation, leukocyte adhesion, smooth muscle cell proliferation, and antioxidant capacity. Hence, abnormality in NO availability results in generalized accelerated atherosclerosis, hyperfiltration, glomerulosclerosis, tubulointerstitial fibrosis and progressive decline in glomerular filtration rate, and apoptosis and neovascularization in the retina. Indeed, the parallel development of nephropathy, retinopathy, and macroangiopathy may be considered as manifestations of endothelial dysfunction at distinct vascular sites. Given this scenario, intervention targeting any of the pathways involved in the NOS/NO system cascade may prove potential therapeutic targets in the prevention of long-term diabetic complications.

Key words

Diabetes - Nephropathy - Retinopathy - Macroangiopathy - Endothelial dysfunction

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F. Chiarelli, M. D.

Department of Pediatrics

University of Chieti · Ospedale Policlinico · Via dei Vestini 5 · 66100 Chieti · Italy

Phone: +39(871)358015

Fax: +39(871)574831

Email: chiarelli@unich.it