Protective effects of cariporide on endothelial dysfunction induced by high glucose
Abstract
Aim: To explore the effects of cariporide, a selective sodium-hydrogen antiporter
inhibitor, on endothelial dysfunction induced by high glucose. Methods: Acetylcholine
(ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside
(SNP)-induced endothelium-independent relaxation and biochemical parameters
including malondialdehyde (MDA), superoxide dismutase (SOD), and
nitric oxide (NO) were measured in rat isolated aorta. Results: A 6-h incubation
of aortic rings with high glucose (44 mmol/L) resulted in a significant inhibition
of EDR, but had no effects on endothelium-independent relaxation. After the 6-h
incubation of aortic rings in the co-presence of cariporide (0.01, 0.1, and 1 μmol/L)
with high glucose, cariporide prevented the inhibition of EDR caused by high
glucose in concentration-dependent manners. Similarly, high glucose decreased
SOD activity and contents of NO, and increased MDA concentration in aortic
tissue. Cariporide (1 μmol/L) significantly resisted the decrease of NO content
and SOD activity, and elevation of MDA concentration caused by high glucose in
aortic tissues. Mannitol (44 mmol/L) or cariporide (1 μmol/L) alone had no effect
on EDR, endothelium-independent relaxation and biochemical parameters.
Conclusion: Cariporide significantly prevented endothelial dysfunction induced
by high glucose. The mechanisms of endothelial dysfunction induced by high
glucose may involve the activation of sodium-hydrogen antiporter and the generation
of oxygen-free radicals, but it is not related to the change of osmolarity.
Keywords:
inhibitor, on endothelial dysfunction induced by high glucose. Methods: Acetylcholine
(ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside
(SNP)-induced endothelium-independent relaxation and biochemical parameters
including malondialdehyde (MDA), superoxide dismutase (SOD), and
nitric oxide (NO) were measured in rat isolated aorta. Results: A 6-h incubation
of aortic rings with high glucose (44 mmol/L) resulted in a significant inhibition
of EDR, but had no effects on endothelium-independent relaxation. After the 6-h
incubation of aortic rings in the co-presence of cariporide (0.01, 0.1, and 1 μmol/L)
with high glucose, cariporide prevented the inhibition of EDR caused by high
glucose in concentration-dependent manners. Similarly, high glucose decreased
SOD activity and contents of NO, and increased MDA concentration in aortic
tissue. Cariporide (1 μmol/L) significantly resisted the decrease of NO content
and SOD activity, and elevation of MDA concentration caused by high glucose in
aortic tissues. Mannitol (44 mmol/L) or cariporide (1 μmol/L) alone had no effect
on EDR, endothelium-independent relaxation and biochemical parameters.
Conclusion: Cariporide significantly prevented endothelial dysfunction induced
by high glucose. The mechanisms of endothelial dysfunction induced by high
glucose may involve the activation of sodium-hydrogen antiporter and the generation
of oxygen-free radicals, but it is not related to the change of osmolarity.