Blunted response to systemic nitric oxide synthase inhibition in the cerebral circulation of patients with Type 2 diabetes

Nazir, Fozia; Alem, Manal M.; Small, M.; Connell, John; Lees, Kennedy R.; Walters, Matthew; Cleland, Stephen J.

doi:10.1111/j.1464-5491.2006.01815.x

Cited by 31 publications

(26 citation statements)

References 21 publications

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“…A recent study found a decreased response of cerebrovascular blood flow to NO synthase inhibition in diabetic patients compared with nondiabetic patients, although not enough patients were enrolled to determine significance (98). In addition, parasympathetic neurons that secrete NO into the perivascular space have been documented to degenerate and eventually die in the absence of insulin signaling (99).…”

Section: Endothelial Dysfunction and Nitricmentioning

confidence: 99%

Diabetes, the Metabolic Syndrome, and Ischemic Stroke

2007

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Section: Endothelial Dysfunction and Nitricmentioning

confidence: 99%

Diabetes, the Metabolic Syndrome, and Ischemic Stroke

2007

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“…Direct effects of hyperglycaemia on the vasculature include endothelial dysfunction [28], reduced vascular reactivity [29], inflammation and thrombosis [30]. In diabetics, reduced endothelial nitric oxide production results in a blunted cerebral vasodilation response to an ischaemic insult and may compromise blood flow to peripheral penumbral areas [28].…”

Section: Pathology Of Pshmentioning

confidence: 99%

“…In diabetics, reduced endothelial nitric oxide production results in a blunted cerebral vasodilation response to an ischaemic insult and may compromise blood flow to peripheral penumbral areas [28]. Acute hyperglycaemia may also attenuate nitric oxide-driven cerebral vasodilation through production of reactive oxygen species [31].…”

Section: Pathology Of Pshmentioning

confidence: 99%

Hyperglycaemia in Acute Stroke – To Treat or Not to Treat

Quinn

Lees²

2009

Cerebrovasc Dis

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Diabetes is common amongst patients with stroke and is associated with poorer outcome. Post-stroke hyperglycaemia is also recognised in up to half of the patients, and is independently associated with adverse sequelae: both increased mortality and poorer functional outcomes. Neither the aetiology nor the pathophysiology of such hyperglycaemia is fully understood. Both direct neurological toxicity and systemic consequences are postulated to occur. A distinction between occult diabetes and non-diabetic hyperglycaemia seems important as prognosis and effect of intervention differ in these two groups. The optimal management of the milder forms of hyperglycaemia associated with acute stroke is unknown. Randomised trial data remain limited but presently offer no strong support for aggressive intervention in stroke, though in other critical illness settings tight control of blood sugar appears beneficial. Studies based in coronary care and high dependency units have shown a possible beneficial effect of insulin, but evidence for intervention in acute stroke is at best limited. However, if glucose management is to be undertaken, this should be instituted while there is still salvageable tissue and the glucose reduction must be substantial. Intravenous insulin may be more effective than glucose-potassium-insulin infusion. Both interventions carry a risk of hypoglycaemia and any proposed intervention must balance safety, convenience and glycaemic control. Until further trial data are available, consensus guidelines may be followed, which are generally conservative for blood glucose levels below 10 mM (180 mg/dl).

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“…Along with these effects, advanced glycation end products induce an increase in inflammatory cytokines like tumor-necrosis factor-α and interlekin-1, which causes a decrease in endothelium dependent vasodilation and an increase in VSMC migration and proliferation (62), further contributing to the development of the pro-atherogenic state. This endothelial dysfunction in T2D can potentially explain the reductions in CBF observed in patients, as was shown in a clinical study by Nazir et al (63) where assessment of decreased CBF revealed that basal NO activity is attenuated in the cerebral circulation of established T2D patients.…”

Section: Introductionmentioning

confidence: 70%

Cerebrovascular complications of diabetes: focus on cognitive dysfunction

2016

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The incidence of diabetes has more than doubled in the United States in the last 30 years and the global disease rate is projected to double by 2030. Cognitive impairment has been associated with diabetes, worsening quality of life in patients. The structural and functional interaction of neurons with the surrounding vasculature is critical for proper function of the central nervous system including domains involved in learning and memory. Thus, in this review we explore cognitive impairment in patients and experimental models, focusing on links to vascular dysfunction and structural changes. Lastly, we propose a role for the innate immunity--mediated inflammation in neurovascular changes in diabetes.

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Blunted response to systemic nitric oxide synthase inhibition in the cerebral circulation of patients with Type 2 diabetes

Abstract: Response to NOS inhibition is impaired in the cerebral circulation of patients with diabetes. This observation is consistent with the elevated cerebrovascular risk reported in this population, and may represent a future therapeutic target in stroke prevention.

Cited by 31 publications

References 21 publications

Diabetes, the Metabolic Syndrome, and Ischemic Stroke

Diabetes, the Metabolic Syndrome, and Ischemic Stroke

Hyperglycaemia in Acute Stroke – To Treat or Not to Treat

Cerebrovascular complications of diabetes: focus on cognitive dysfunction

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