Impairment of endothelium‐dependent but not of endothelium‐independent dilatation in guinea‐pig aorta rings incubated in the presence of elevated glucose

Abstract

1 Purine compounds such as ATP and adenosine, respectively endothelium-dependent and -independent vasodilators, are largely involved in the control of vascular tone and vascular reactivity to contracting stimuli. We investigated the relaxing activity of ATP and adenosine in guinea-pig aorta rings exposed for 6 h to elevated glucose concentration (50 mM), in order to mimic hyperglycaemic conditions. Guinea-pigs were reserpine-treated (2 mg kg 71 , i.p., 48 and 24 h before death). 2 Rings of aortae incubated in 50 mM glucose, contracted submaximally by 1 mM noradrenaline, lost endothelium-dependent relaxation in response to acetylcholine (10 nM to 10 mM). Aortae incubated with 50 mM mannose, as a hyperosmotic control, relaxed to acetylcholine normally. Rings of aortae incubated in 50 mM glucose, contracted submaximally by 3 mM 4-aminopyridine, lost endothelium-dependent relaxation in response to ATP (30 mM) whereas endothelium-independent relaxation in response to adenosine (0.3 mM) was well preserved. 4 The relaxation induced by A23187 or sodium nitroprusside (10 nM to 0.1 mM) did not di er between rings exposed to control (5.5 mM) or elevated glucose (50 mM) and contracted submaximally by 3 mM 4-aminopyridine. 5 When incubated with aortic tissue in the presence of elevated glucose, the cyclo-oxygenase inhibitors, indomethacin (10 mM) and mefenamic acid (30 mM), or the scavenger of superoxide anions, superoxide dismutase (150 u ml 71 ), prevented the impairment of ATP-mediated relaxation. 6 The present results indicate that endothelium-dependent, receptor-induced relaxation in response to acetylcholine and ATP is impaired in guinea-pig aorta rings exposed to elevated glucose. The endothelial dysfunction caused by glucose might be located at a step between receptor activation and intracellular calcium increase, and might be related to an increased metabolism of arachidonic acid coupled to an increased production, or to a reduced inactivation of superoxide anions.

Early and intermediate Amadori glycosylation adducts, oxidative stress, and endothelial dysfunction in the streptozotocin-induced diabetic rats vasculature

“…Furthermore, 1 week after introduction of insulin treatment glycaemia was below normal values but endothelial dysfunction was still present. These results disagree with studies reporting an impairment of endothelial function in vessels from non-diabetic animals incubated in very high concentrations of glucose (20 to 50 mmol/l) [18,19,20,21,22,23,24]. Nevertheless, in agreement with our findings, other authors have reported a good preservation of endothelial relaxations in short-term diabetes (1 week) induced by streptozotocin in rats [53], or after subacute (1 day) hyperglycaemia in humans [54].…”

“…Some authors indicate that increased glucose itself is a source of free radicals that leads to endothelium dysfunction [18,19,20,21,22,23,24]. Our results, however, clearly indicate that high glucose by itself is not directly related to the impairment of endothelium-dependent relaxations.…”

“…However, the specific mechanisms linking hyperglycaemia with oxidative stress and endothelial dysfunction are not well understood. Some authors suggest that increased blood glucose concentrations directly produce oxidative stress and endothelium impairment [18,19,20,21,22,23,24]. Other investigators propose that hyperglycaemia can modify different enzymatic pathways, which produce oxidative stress and cause the alterations of endothelium.…”

Effects of diabetes and treatment with the antioxidant α-lipoic acid on endothelial and neurogenic responses of corpus cavernosum in rats

“…In some other vascular tissues, effects to short-term glucose exposure are similar to those of diabetes. Thus, in rabbit and guinea pig aorta, high glucose effects are linked to ROS-stimulated endothelial release of a prostanoid vasoconstrictor which opposes ACh-induced relaxation [59,60]. A similar effect was noted for rat mesenteric resistance vessels, combined with depression of endothelium derived hyperpolarising factor mediated responses [61].…”

Lipoflavon® application for pharmacological correction of endothelial dysfunction in diabetic rats

“…Хоча збільшення часу інку-бації до 6 год призводило до зниження ендотелійзалежної дилатації і у судинних сег-ментів грудної аорти самців [16,39]. При цьому ендотелійнезалежна вазодилатація (Na-нітропрусид, A23187) не зазнавала змін після 6 год інкубації за високих концен-трацій глюкози (44 мМ, 50 мМ) сегмен тів аорти як щурів, так і мурчаків обох статей [12,39].…”