Endothelial nitric oxide synthase enhancer for protection of endothelial function from asymmetric dimethylarginine-induced injury in human internal thoracic artery

The Journal of Thoracic and Cardiovascular Surgery
Chao XuanJing-Song Ou

Abstract

Endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine is a cardiovascular risk factor that is elevated in patients with coronary artery disease. We hypothesized that novel endothelial nitric oxide synthase enhancer AVE3085 might improve the endothelial function altered by asymmetric dimethylarginine in the human internal thoracic artery. Cumulative concentration-relaxation curves to acetylcholine (-11 to -5 log mol/L) were established in left internal thoracic artery rings (n = 65) from 27 patients undergoing coronary artery bypass grafting in precontraction induced by U46619 (-8 log mol/L) in the absence or presence of asymmetric dimethylarginine (100 μmol/L) or AVE3085 (30 μmol/L). Protein expressions of endothelial nitric oxide synthase and levels of superoxide anion production were detected. Maximal relaxation induced by acetylcholine was significantly attenuated by asymmetric dimethylarginine (12.7% ± 2.3% vs 35.3% ± 5.0% in control; P < .05) and significantly restored by AVE3085 (23.4% ± 2.8%; P < .05). AVE3085 also markedly restored endothelial nitric oxide synthase expression (0.29 ± 0.008; P = .012) reduced by asymmetric dimethylarginine (0.05 ± 0.04 vs 0.36 ± 0.03 in control; P = .014). Increased supe...Continue Reading

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Citations

Oct 25, 2016·The Journal of Thoracic and Cardiovascular Surgery·Takeshi KinoshitaTomio Okamura
Jun 29, 2017·Journal of Cellular Biochemistry·Abbas Mohammadpour-GharehbaghMojgan Mokhtari
Feb 7, 2013·American Journal of Physiology. Endocrinology and Metabolism·Hong-Bo CiJing-Song Ou
Jan 31, 2021·Interactive Cardiovascular and Thoracic Surgery·Gábor VeresGábor Szabó

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