Reactive oxygen species contribute to sleep apnea-induced hypertension in rats.
In clinical studies, sleep apnea is associated with hypertension, oxidative stress, and increased circulating endothelin-1 (ET-1). We previously developed a model of sleep apnea by exposing rats to eucapnic intermittent hypoxia (IH-C) during sleep, which increases both blood pressure and plasma levels of ET-1. Because similar protocols in mice increase tissue and plasma markers of oxidative stress, we hypothesized that IH-C generation of reactive oxygen species (ROS) contributes to the development of ET-1-dependent hypertension in IH-C rats. To test this, male Sprague-Dawley rats were instrumented with indwelling blood pressure telemeters and drank either plain water or water containing the superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl, 1 mM). Mean arterial pressure (MAP) and heart rate (HR) were recorded for 3 control days and 14 treatment days with rats exposed 7 h/day to IH-C or air/air cycling (Sham). On day 14, MAP in IH-C rats treated with Tempol (107 +/- 2.29 mmHg) was significantly lower than in untreated IH-C rats (118 +/- 9 mmHg, P < 0.05). Tempol did not affect blood pressure in sham-operated rats (Tempol = 101 +/- 3, water = 101 +/- 2 mmHg). Immunoreactive ET-1 was greater in plasma from IH-C rats compared with plasma from sham-operated rats but was not different from Sham in Tempol-treated IH-C rats. Small mesenteric arteries from IH-C rats but not Tempol-treated IH-C rats had increased superoxide levels as measured by ferric cytochrome c reduction, lucigenin signaling, and dihydroethidium fluorescence. The data show that IH-C increases ET-1 production and vascular ROS levels and that scavenging superoxide prevents both. Thus oxidative stress appears to contribute to increases in ET-1 production and elevated arterial pressure in this rat model of sleep apnea-induced hypertension.
Troncoso Brindeiro
Carmen M
CM
Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, NM 87131, USA.
da Silva
Ana Q
AQ
Allahdadi
Kyan J
KJ
Youngblood
Victoria
V
Kanagy
Nancy L
NL
D000818:Animals; D019332:Endothelin-1 / Q000378:metabolism*; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012891:Sleep Apnea Syndromes / Q000150:complications* / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*
D019332:Endothelin-1; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase