Aim: 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.
Conclusion: 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.