Dual vascular effects of leptin via endothelium: hypothesis and perspective.

Secreted by adipocytes, leptin is a hormone which regulates appetite and metabolism. Leptin secretion is proportional to the fat mass, and thus leptin concentration is raised in most obese subjects. In recent years, more and more biological effects have been attributed to leptin; one of the most well-known effects is the effect of leptin on the vascular tone. Obesity is very often associated with hypertension, and it has been known that leptin affects the blood pressure by activating the sympathetic nervous system and causing endothelial cell (EC) dysfunction. However, there has been strong evidence that leptin is able to dilate blood vessels. Such vasodilation has been shown to be EC-dependent and EC-independent. Further, both nitric oxide-dependent and nitric oxide-independent mechanisms have been reported. In this mini-review, we summarize the heterogeneous mechanisms by which leptin causes relaxation of vascular smooth muscle. We also argue that while leptin may act as a direct dilator on the vasculature in healthy subjects, hyperleptinemia in obese subjects gradually dysregulates blood pressure control by deteriorating EC functions. How these dual effects of leptin on EC might be related to EC ionic channels is also discussed.