Obstructive sleep apnea (OSA) causes intermittent
hypoxia (IH) associated with
hypertension,
insulin resistance and a systemic inflammatory response. We evaluated the effects of
melatonin on vasodilation, capillary perfusion in hamster cheek pouch and
insulin resistance,
hypertension, and
reactive oxygen species (ROS) and
nitrate/
nitrite levels after IH for 4 wk. Syrian hamsters were divided into four groups: control group (CON), IH group, and
melatonin (10 mg/kg) intraperitoneally administered daily for 4
wk/30 min before intermittent air (MEL) or IH (IH + MEL) exposure. IH alone caused elevated blood pressure, increased hematocrit, fasting
hyperglycemia, elevated ROS and
nitrite/
nitrate levels, and vasoconstriction and reduced microvascular perfusion.
Melatonin treatment of IH-exposed animals decreased blood pressure,
blood glucose, and ROS and
nitrite/
nitrate levels, and increased vasodilation and capillary perfusion. An oral
glucose tolerance test was performed after 4 wk of IH. During the last 30 min of the hyperinsulinemic euglycemic clamp,
blood glucose, and
insulin levels were identically matched between groups, but the
glucose infusion rate was significantly reduced in IH (29.9 +/- 1.9 mg/kg/min) versus IH + MEL group (45.4 +/- 1.5 mg/kg/min, P < 0.05) demonstrating a decrease in
insulin sensitivity. These results suggest that ROS and
nitrite/
nitrate levels play important roles in the microvascular dysfunction in IH and that this process is attenuated by
melatonin. In conclusion, protection induced by
melatonin against functional and metabolic impairment in IH is related to the regulation of ROS and
nitrite/
nitrate levels in the microcirculation. These observations may have importance to OSA pathological changes.