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- W2364265135 abstract "Background There are considerable controversies over the adverse effects of hyperglycemia and tight glucose control on cardiovascular outcomes in type 2 diabetes patients.ObjectiveThis study compared aortic endothelium-dependent vasodilation between obese type 2 diabetic Otsuka Long-Evans Tokushima Fatty(OLETF)rats and non-obese diabetic Goto-Kakizaki(GK)rats.The roles of insulin in endothelium-dependent vasodilation,as well as the mechanism of hyperglycemia/hyperosmolarity in relation to endothelial nitric oxide synthase(eNOS)/heme oxygenase(HO),was examined.Methods① The thoracic aortae from both OLETF and GK rats of 24 weeks were isolated and vasodilatory function was assessed in vitro.Segments of the aortae were used for eNOS/HO determination with immunofluorescence.② One group of GK rats were injected with insulin for 10 d before observing vasodilatory function and ultrastructure of the intima.③Normal aortic segments were incubated in the buffer of hyperglycemia or hyperosmolarity(by adding 50 mmol/L glucose or mannitol to Krebs-Henseleit buffer,350 mOsm/L)for 5 h and contents of eNOS/HO were examined with Western blotting.Results① Compared with non-diabetic controls,blood glucose levels of both OLETF and GK rats were significantly elevated,with the level of GK rats higher than that of OLETF rats GK(15.6±2.5)mmol/L vs OLETF(9.9±0.4)mmol/L,P0.01.Serum insulin level in OLETF rats was higher than that of GK rats OLETF(11.5±1.2)vs GK(2.1±0.2)μg/L,P0.01.② While OLETF rats' aortae showed significantly reduced endothelium-dependent vasodilation with decreased eNOS level,GK had enhanced vasodilation with increased eNOS and HO.The endothelium-dependent vasodilation in OLETF could be blocked completely by the inhibition of eNOS,while concomitant blockade of eNOS and HO was indispensable for complete inhibition of endothelium-dependent vasodilation in GK rats.③ Insulin administration for GK rats induced dramatic intimal hyperplasia and diminished endothelium-dependent vasodilation,which was accompanied by significant eNOS/HO reduction.④ Hyperglycemia and hyperosmolarity with mannitol resulted in eNOS/HO elevation.ConclusionEndothelium-dependent vasodilation was reduced in hyperinsulinemic obese OLETF rats and enhanced in severely hyperglycemic non-obese GK rats.Insulin administration weakened the enhanced vasodilation in GK rats and promoted intimal hyperplasia.Marked hyperglycemia/hyperosmolarity may play a role in the regulation of vasodilation in GK rats by inducing eNOS/HO's up-regulation." @default.
- W2364265135 created "2016-06-24" @default.
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- W2364265135 date "2011-01-01" @default.
- W2364265135 modified "2023-09-24" @default.
- W2364265135 title "Changes of endothelium-dependent vasodilation in aortae from obese and non-obese type 2 diabetic rats and the roles of hyperglycemia/hyperosmolarity" @default.
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