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.
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Najemnik C, Sinzinger H, Kritz H . Endothelial dysfunction, atherosclerosis and diabetes. Acta Med Austriaca 1999; 26: 148–53.
Guo X, Liu WL, Chen LW, Guo ZG . High glucose impairs endothelium-dependent relaxation in rabbit aorta. Acta Pharmacol Sin 2000; 21: 169–73.
Pieper GM . Enhanced, unaltered and impaired nitric oxide-mediated endothelium-dependent relaxation in experimental diabetes mellitus: importance of disease duration. Diabetologia 1999; 42: 204–13.
Friesen NT, Buchau AS, Schott-Ohly P, Lgssiar A, Gleichmann H . Generation of hydrogen peroxide and failure of antioxidative responses in pancreatic islets of male C57BL/6 mice are associated with diabetes induced by multiple low doses of streptozotocin. Diabetologia 2004; 47: 676–85.
Matteucci E, Giampietro . Sodium/hydrogen exchange activity in type 1 diabetes mellitus: the never-ending story. Diabetes Nutr Metab 2001; 14: 225–33.
Ganz MB, Hawkins K, Reilly RF . High glucose induces the activity and expression of Na+/H+ exchange in glomerular mesangial cells. Am J Physiol Renal Physiol 2000; 278: F91–6.
Tu JH, Liu LY, Zhang XH . Protective effect of Na+/H+ exchanger inhibitor cariporide on the injury of vascular endothelial function induced by hypercholesterolemia. Bull Hu-nan Med Univ 2002; 27: 13–6.
Ma FX, Liu LY, Xiong XM . Protective effects of lovastatin on vascular endothelium injured by low density lipoprotein. Acta Pharmacol Sin 2003; 24: 1027–32.
Tesfamariam B, Brown ML, Cohen RA . Elevated glucose impaired endothelium-dependent relaxation by activating protein kinase C. J Clin Invest 1991; 87: 1643–8.
Xu B, Rao MR . High concentration of glucose inhibits endothelium-dependent vasorelaxation of rabbit aortic artery. Acta Pharmacol Sin 2001; 22: 861–4.
Guo X, Liu WL, Chen LW, Guo ZG . High glucose enhances H2O2-induced apoptosis in bovine aortic endothelial cells. Acta Pharmacol Sin 2000; 21: 41–5.
Jandeleit-Dahm K, Hannan KM, Farrelly CA, Allen TJ, Rumble JR, Gilbert RE, et al. Diabetes-induced vascular hypertrophy is accompanied by activation of Na+/H+ exchange and prevented by Na+/H+ exchange inhibition. Circ Res 2000; 87: 1133–40.
Telejko B, Tomasiak M, Stelmach H, Kinalska I . Platelet sodium-proton exchanger and phospholipid-dependent procoagulant activity in patients with type 2 diabetes. Metabolism 2003; 52: 102–6.
Williams B, Howard RL . Glucose-induced changes in Na+/H+ antiport activity and gene expression in cultured vascular smooth muscle cells. Role of protein kinase C. J Clin Invest 1994; 93: 2623–31.
Siczkowski M, Ng LL . Glucose-induced changes in activity and phosphorylation of the Na+/H+ exchanger, NHE-1, in vascular myocytes from Wistar-Kyoto and spontaneously hypertensive rats. Metabolism 1996; 45: 114–9.
Scholz W, Albus U, Counillon L, Gogelein H, Lang HJ, Linz W, et al. Protective effects of HOE642, a selective sodium-hydrogen exchange subtype 1 inhibitor, on cardiac ischaemia and reperfusion. Cardiovasc Res 1995; 29: 260–8.
Teshima Y, Akao M, Jones SP, Marban E . Cariporide (HOE642), a selective Na+/H+ exchange inhibitor, inhibits the mitochondrial death pathway. Circulation 2003; 108: 2275–81.
Cutaia M, Kroczynski J, Tollefson K . pH-dependent oxidant production following inhibition of the mitochondrial electron transport chain in pulmonary endothelial cells. Endothelium 2002; 9: 109–21.
Svegliati-Baroni G, Di Sario A, Casini A, Ferretti G, D'Ambrosio L, Ridolfi F, Bolognini L, et al. The Na+/H+ exchanger modulates the fibrogenic effect of oxidative stress in rat hepatic stellate cells. J Hepatol 1999; 30: 868–75.
Stromer H, de Groot MC, Horn M, Faul C, Leupold A, Morgan JP, et al. Na+/H+ exchange inhibition with HOE642 improves postischemic recovery due to attenuation of Ca2+ overload and prolonged acidosis on reperfusion. Circulation 2000; 101: 2749–55.
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Project supported by the National Natural Science Foundation of China (No 39770857).
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Wang, Sx., Xiong, Xm., Song, T. et al. Protective effects of cariporide on endothelial dysfunction induced by high glucose. Acta Pharmacol Sin 26, 329–333 (2005). https://doi.org/10.1111/j.1745-7254.2005.00042.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00042.x
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