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J Clin Pharmacol. 2013 Dec;53(12):1228-39. doi: 10.1002/jcph.179. Epub 2013 Sep 30.

Obesity impairs vasodilatation and blood flow increase mediated by endothelial nitric oxide: an overview.

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  • 1Toyama Institute for Cardiovascular Pharmacology Research, Osaka, Japan; Department of Pharmacology, Shiga University of Medical Science, Shiga, Japan.


Obesity dramatically increases the risk of development of cardiovascular and metabolic diseases. Endothelial dysfunction induced by obesity is an important risk factor that impairs blood flow controls in various organs. Impaired endothelial function occurs early in life in obese children. Obesity-induced endothelial dysfunction is associated with decreased nitric oxide (NO) production due to impaired endothelial NO synthase activity and expression and increased production of superoxide anion and the endogenous NOS inhibitor ADMA, together with increased vasoconstrictor factors, such as endothelin-1 and sympathetic nerve activation. Decreased endothelial progenitor cells are also involved in endothelial cell senescence in obese individuals. Insulin resistance and diabetes mellitus augment obesity-induced endothelial dysfunction. Adipokines liberated from adipose tissues play roles in modulating endothelial function; adiponectin and ghrelin have beneficial effects on endothelial cells. Effects of leptin on endothelial function are controversial. Decreased body weight by physical exercise, dietary interventions, and bariatric surgery are effective measures that reverse endothelial dysfunction; however, the weight control is not only the reason for improving of endothelia function. Pharmacological therapies with β-adrenoceptor antagonists, resveratolol, anti-obesity agents, nifedipine, and NADPH oxidase inhibitors may also be effective; however, these treatments have to be utilized under the basis of exercise and dietary controls.

© 2013, The American College of Clinical Pharmacology.


adipokine; endothelium-dependent vasodilatation; nitric oxide; obesity; pharmacological treatment

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