| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, New Mexico, United States
2 Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, New Mexico, United States; Departament de Fisiologia e Biofisica, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
3 Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, United States
4 Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States
* To whom correspondence should be addressed. E-mail: nkanagy{at}salud.unm.edu.
In clinical studies, sleep apnea is associated with hypertension, oxidative stress and increased circulating endothelin (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 (4-2,2,6,6-tetramethyl-piperidine 1-oxyl, 1mM). Mean arterial pressure (MAP) and heart rate (HR) were recorded for 3 control days and 14 treatment days with rats exposed 7 hrs/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 rats (tempol=101±3, water=101±2). Immunoreactive ET-1 was greater in plasma from IH-C rats compared to plasma from Sham 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.
This article has been cited by other articles:
|
|
 |
|
  B. J. Morgan Intermittent hypoxia: keeping it real J Appl Physiol, July 1, 2009; 107(1): 1 - 3. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Lavie and P. Lavie Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link Eur. Respir. J., June 1, 2009; 33(6): 1467 - 1484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Belaidi, M. Joyeux-Faure, C. Ribuot, S. H. Launois, P. Levy, and D. Godin-Ribuot Major role for hypoxia inducible factor-1 and the endothelin system in promoting myocardial infarction and hypertension in an animal model of obstructive sleep apnea. J. Am. Coll. Cardiol., April 14, 2009; 53(15): 1309 - 1317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Wilcox and A. Pearlman Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides Pharmacol. Rev., December 1, 2008; 60(4): 418 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Allahdadi, T. W. Cherng, H. Pai, A. Q. Silva, B. R. Walker, L. D. Nelin, and N. L. Kanagy Endothelin type A receptor antagonist normalizes blood pressure in rats exposed to eucapnic intermittent hypoxia Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H434 - H440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. Soukhova-O'Hare, R. V. Ortines, Y. Gu, A. D. Nozdrachev, S. D. Prabhu, and D. Gozal Postnatal Intermittent Hypoxia and Developmental Programming of Hypertension in Spontaneously Hypertensive Rats: The Role of Reactive Oxygen Species and L-Ca2+ Channels Hypertension, July 1, 2008; 52(1): 156 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Allahdadi, L. C. Duling, B. R. Walker, and N. L. Kanagy Eucapnic intermittent hypoxia augments endothelin-1 vasoconstriction in rats: role of PKC{delta} Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H920 - H927. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
