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5 CHRONIC LEPTIN STIMULATION DOES NOT MODULATE NITRIC OXIDE RELEASE FROM HUMAN AORTIC ENDOTHELIAL CELLS.
  1. A. S. Graves1,2,
  2. D. Kleinhenz1,2,
  3. J. Hwang1,2,
  4. C. M. Hart1,2
  1. 1Atlanta VAMC, Decatur, GA
  2. 2Emory University, Atlanta, GA

Abstract

Acute exposure to the adipokine leptin has been shown to stimulate endothelial nitric oxide (NO) production. However, obesity and other states associated with chronic hyperleptinemia are often characterized by endothelial dysfunction and impaired NO bioavailability. Therefore, we hypothesized that chronic exposure to pathophysiologic leptin levels would decrease NO bioavailability. To test this hypothesis, human aortic endothelial cells (HAECs) were treated with graded concentrations of leptin (5-60 ng/mL) for 72 hours. Endothelial NO production, detected by chemiluminescence analysis of NO and its oxidation products in culture media, cyclic guanosine monophosphate (cGMP) activity, and endothelial nitric oxide synthase (eNOS) activity, was similar to control for all concentrations of leptin studied. Leptin had no effect on eNOS expression assessed with Western blotting and calculated relative to actin expression (n = 7). Because superoxide reacts at diffusion limited rates with NO and reduces its bioavailability, we examined NADPH oxidase and xanthine oxidase, two major sources of superoxide generation in vascular endothelial cells. Chronic leptin exposure did not alter the expression of Nox-4, gp91phox, p22phox, or p67phox, all important components of the NADPH oxidase electron transfer complex in human endothelial cells (n = 5). Similarly, the expression of xanthine oxidase was unchanged when all concentrations of leptin exposures were compared (n = 6). In conclusion, chronic leptin exposure even at pathophysiologic levels does not modulate endothelial NO bioavailability and is not associated with increased superoxide anion production via NADPH oxidase activity.

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