High glucose impairs endothelium-dependent relaxation in rabbit aorta.
OBJECTIVE
To study the effects of high glucose on endothelium-dependent relaxation (EDR) and the action of L-arginine, superoxide dismutase (SOD), or glucose re-normalization in aorta.


METHODS
Measurement of EDR of the isolated rabbit thoracic aortic rings.


RESULTS
Elevated glucose (25 mmol.L-1) caused profound impairment of acetylcholine (ACh)-induced relaxation, EC50: 1.6 mumol.L-1 (95% CL: 7.9 nmol.L(-1)-6.3 mumol.L-1) vs normal glucose (5.5 mmol.L-1) EC50: 0.08 mumol.L-1 (95% CL: 0.02 mumol.L(-1)-0.3 mumol.L-1) (P < 0.01), which not reversed followed by a further 24 h incubation in normal glucose M199, EC50: 2.0 mumol.L-1 (95% CL: 0.2 pmol.L(-1)-12.5 mumol.L-1). However, aortic rings incubated with mannitol (19.5 mmol.L-1) relaxed to ACh normally. L-arginine 1 mmol.L-1 or SOD 150 U.L-1 restored ACh relaxation in elevated glucose to normal, EC50: 0.16 mumol.L-1 (95% CL: 0.04 mumol.L(-1)-0.8 mumol.L-1) and 0.16 mumol.L-1 (95% CL: 0.03-0.63 mumol.L-1). The relaxation in response to sodium nitroprusside was not different between rings exposed to normal or elevated glucose.


CONCLUSIONS
Hyperglycemia impaired EDR, which was not reversible by glucose re-normalization, increased free radical production and altered L-arginine metabolism were involved in this endothelium dysfunction.
Laboratory of Molecular Pharmacology, Hu-nan Medical University, Changsha 410078, China. guozg@public.cs.hn.cn
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D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D001013:Aorta, Thoracic; D001120:Arginine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D009599:Nitroprusside; D001120:Arginine; D013482:Superoxide Dismutase; D005947:Glucose; D000109:Acetylcholine