Nitric oxide and vascular responses in Type I diabetes

Abstract

Diabetic microangiopathy and macroangiopathy are the principal causes of morbidity and mortality in patients with diabetes mellitus [1±3]. Patients with Type I (insulin-dependent) diabetes mellitus have a three to sixfold increased risk of cardiovascular death before the age of 60 compared with non-diabetic subjects [4]. Established risk factors for coronary heart disease (CHD) do not, however, fully explain the increased risk in Type I diabetic patients [5].The vascular endothelium has a key role in maintaining homeostasis of the vasculature through the synthesis of vasoactive substances that modulate vascular tone, inhibit platelet aggregation and vascular smooth muscle cell (VSMC) proliferation [6, 7]. Endothelial dysfunction has been suggested to be an early event in diabetic vascular disease [8, 9]. The discovery of endothelium-derived nitric oxide (NO) in the late 1980 s [10] has considerably improved our understanding in vascular biology and pathogenesis of endothelial dysfunction. With the use of techniques such as brachial artery ultrasonography, venous occlusion plethysmography and brachial artery infusion of endothelium-dependent vasoactive agents, endothelial function can be indirectly assessed in different vascular beds. Most published reviews have focused on Type II (non-insulin-dependent) diabetes mellitus rather than Type I diabetes. We reviewed the current evidence for endothelium-mediated vascular dysfunction in Type I diabetes following an extensive literature search from both Medline and PubMed (1965±1999) using the following keywords:`Type I diabetes mellitus',`endothelial function',`nitric oxide', vasodilatation'. Potential mechanisms which could be involved in endothelial dysfunction in Type I diabetes are discussed. Diabetologia (2000)

Impaired Pressure-Induced Vasodilation at the Foot in Young Adults With Type 1 Diabetes

“…Hyperglycemia could induce increased NO production and reduced NO availability due to inactivation, mediated by free radicals. Recent work suggests that in type 1 diabetes, there could be specific defects in signal transduction mechanisms linked to NO synthase (receptors, ion channels), NO synthase expression, or destruction of NO after it has been produced (36). Skin biopsies from the dorsum of the foot of patients with diabetes have also shown a significant decrease in endothelial NO synthase expression, and this may prove to be the potential cause of reduced endothelial function (29,37).…”

Diabetes potentiates acetylcholine-induced relaxation in rabbit renal arteries

“…mental model of diabetes in the rabbit Chan et al, 2000 . It is generally accepted that endothelium-dependent relaxation is impaired in different vascular beds of several animal species with experimentally induced diabetes mellitus, whereas this endothelium-mediated vasodilatation also Ž appears impaired or unchanged in diabetic patients see, . for review, Sobrevia and Mann, 1997;Chan et al, 2000 . However, there are some reports that show an enhanced endothelium-dependent relaxation in response to histamine Ž . Ž White andCarrier, 1986 andto acetylcholine Bhardwaj .…”

“…The pathophysiological processes underlying vascular complications are still poorly understood. However, in recent years, several lines of evidence have suggested that some of the vascular changes in diabetes may be related to alterations in en-Ž dothelial function see, for review, Chan et al, 2000;De . Vriese et al, 2000 . Endothelial cells are known to play a central role in the regulation of vascular tone both in physiological and pathophysiological conditions through the release of differ-ent vasodilator and vasoconstrictor substances.…”

“…diabetes Yamada et al, 1995 . It seems likely that prolonged exposure to hyperglycaemia may modulate the activity of the L-arginine-NO pathway in diabetes and that dysfunctions in NO synthesis or NO activity could lead to the abnormal endothelium-dependent relaxations observed Ž . in diabetes Sobrevia and Mann, 1997;Chan et al, 2000 . Renal injury in diabetes is associated with vascular alterations. A considerable body of evidence indicates that ( )endothelial dysfunction is closely associated with the de-Ž velopment of diabetic nephropathy in humans Stehouwer .…”

Statin Treatment Decreased Serum Asymmetric Dimethylarginine (ADMA) Levels in Ischemic Stroke Patients

“…In particular, these drugs decrease the risk of vascular events in patients with cardiovascular disease and ischemic stroke irrespective of the baseline LDL-C level 6) . The maintenance of physiological vascular tone and structure depends on endothelial production and the release of nitric oxide (NO) 7) . Asymmetric dimethylarginine (ADMA) was recently characterized as an endogenous, competitive inhibitor of NO synthase and is now considered a novel independent risk factor for endothelial dysfunction 8) .…”