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Abstract Leptin, the product of the ob gene secreted by adipocytes, is a multifunctional peptide hormone, the circulating concentration of which is proportional to fat mass. It has a major influence on body weight and metabolism and is significantly increased in obesity leading to the concept of leptin resistance. Although the hypothalamus is considered to be the main target for leptin it is becoming clear that leptin has actions on other tissues. A potential role for leptin in vascular physiology/pathophysiology is supported by studies demonstrating that leptin leads to sympathoactivation, superoxide production, vascular, calcification, and angiogenesis. Leptin is a vasodilator. The mechanisms underlying this effect are unclear and results of studies in different specie contradictory. In rats, it has been shown that leptin leads to vasorelaxation, an effect, which may occur by activation of PI3K/Akt to stimulate endothelial nitric oxide (NO) synthase. Leptin leads to vasorelaxation by smooth muscle hyperpolarization, whereas a small study in humans did not support a role for NO in leptin’s vascular effects. It has peripheral actions to stimulate vascular inflammation, oxidative stress, and vascular smooth muscle hypertrophy that may contribute to pathogenesis of type 2 diabetes mellitus, hypertension, atherosclerosis, and coronary heart disease. |