Reactive oxygen species contribute to sleep apnea‐induced hypertension in rats

Rats exposed to intermittent hypoxia/hypercapnia (IH/HC) during sleep to mimic sleep apnea have increased mean arterial pressure (MAP) and endothelin 1 (ET‐1). We previously reported that the superoxide dismutase mimetic tempol prevents this increase in blood pressure and circulating ET‐1. Because superoxide (O 2 − ) can stimulate ET‐1 synthesis, we hypothesized that IH/HC increases arterial O 2 − in IH/HC rats to increase ET‐1 and MAP. To test this, rats were exposed to IH/HC or air cycling (Sham) for 14 days. On day 14, mesenteric arteries were dissected and used to evaluate the effect of IH/HC on superoxide generation. Absorbance at 550 mm (Ab 550 ) for ferricytochrome C (FCC, 50 μM) was recorded to determine superoxide production. Ab 550 increased when arteries from either Sham or IH/HC rats were added but Ab 550 was significantly greater in IH/HC than Sham (7.8 ±1.1 vs. 0.2±.001 μM /L, p<.001). Another group of mesenteric arteries were frozen, sectioned and stained with dihydroethidium (DHE) to detect oxidation. DHE staining also demonstrated elevated O 2 − production in IH/HC compared to Sham arteries (583±30 vs 241±10 avg intensity IH/HC vs. Sham, p=.014). In summary, IH/HC appears to increase vascular production of O 2 − . These results support our hypothesis that vascular O 2 − in vivo contributes to ET‐1 synthesis and hypertension in IH/HC‐exposed rats.