Leptin’s Activity on the Hydroxyl Radical: A Possible Link to the Oxidative Stress-Related Endothelial Vasodilation in Patients with Obstructive Sleep Apnea

Abstract

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity, whereas the underlying mechanism is still eluding, the thought participants are chronic intermittent hypoxia with consequent increase in the reactive oxygen species, leading to endothelial cell damage and dysfunction in these patients. As the hydroxyl radical (·OH) mediates the vascular smooth muscle relaxation, identification of its scavengers might reveal sentinel markers of decreased vascular responsiveness and worse long-term comorbid outcome. We therefore assessed leptin's scavenger effect on (∙)OH using the electronic paramagnetic resonance (EPR) method. The (∙)OH was generated by the Fenton reaction in the presence of spin-trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DMPO) with various concentrations of leptin (0.25, 2.5, and 25μg/ml) and without leptin. EPR spectrometer settings were: modulation frequency, 100kHz; X band microwave frequency, 9.5GHz; microwave power, 20mW (milliwatts); modulation amplitude, 1.0G (gauss); time constant, 160s; scan time, 200s; and receiver gain, 1×l0(5). EPR signal intensity between 3,440 and 3,540G of measurements taken in at least three separate experiments was reported. Mannitol, a known (∙)OH scavenger, at 100mM significantly decreased the DMPO-OH adduct formation and was used as the active-control agent. Leptin added to aqueous solutions at all concentrations was associated with a statistically significant decrease in EPR signal compared with controls due to its scavenging activity towards the ·OH. Leptin could be further investigated as a sentinel biomarker of decreased vascular responsiveness and future risk of atherosclerotic disease in obese OSA patients.